Degenerative Osteoarthritis Research Articles

A single-centre RetrospeCtive sTudy Investigating patient-reported outcomeS of extended dressing wear time for incisional healing following orthopaedic surgery: the ARCTIS study.

Orthopaedic surgery is an effective intervention for treating the symptoms of degenerative joint disease or osteoarthritis (OA). Frequent wound dressing changes, unless clinically indicated, can disrupt the healing process and increase the occurrence of incision site contamination. Protection from contamination is critical for surgical incisions and, therefore, undisturbed wound healing (UWH) in surgical wound management is vital. This article describes a retrospective study reporting the clinical performance of a self-adherent, absorbent postoperative dressing, with a focus on dressing wear time. A single-centre, retrospective electronic medical record review of a convenience sample of adult patients treated with a dressing (Mepilex Border Post Op; Mölnlycke, Sweden) following elective hip or knee replacement was undertaken. Data relating to dressing wear time, rationale for dressing changes and patient-reported outcomes were extracted from a mobile health application moveUP Therapy (moveUP NV, Belgium). Health-related quality of life assessment was conducted using the EQ-5D-5L questionnaire and orthopaedic-specific quality of life (QoL) indicator tools. Of the 558 records reviewed, 151 respondents (27.1%) reported outcomes relating to dressing wear time and frequency of dressing change. The average wear time of the first dressing was 13.6 days (second dressing: 5.3 days). The proportion of patients who wore the first dressing for 1-7 days, 8-13 days and for ≥14 days was 17.2%, 13.2% and 69.5%, respectively. Data from the completed questionnaires revealed improvement in QoL over time. The results of this study are a good indicator of the suitability of the postoperative dressing for a 14-day wear time, in line with the principles of UWH.

An Advanced Case of TMJ Osteoarthritis

Advanced temporomandibular joint (TMJ) osteoarthritis can present with several complications, including synovial cyst formation. Through this work , we present a case of a 69-year-old patient with bilateral painful swelling in the parotid regions, he previously operated for goiter in 2003 without any complications. Magnetic resonance imaging (MRI) revealed bilateral temporomandibular joint effusion with a cystic formation on the left, extending from the posterior border of the masseter muscle to the anterior margin of the superficial lobe of the parotid gland, communicating with the joint space. Additionally, there were findings of TMJ irregularities, condylar degeneration, and contrast-enhancing synovial thickening indicative of osteoarthritis. Computed tomography (CT) complement highlighted bilateral condylar flattening with joint space narrowing and osteoarthritic changes

Longitudinal measurement of serum cartilage oligomeric matrix protein can detect the progression of cartilage degeneration in anterior cruciate ligament reconstruction patients

Background/objectiveCartilage oligomeric matrix protein (COMP) has utility as a diagnostic marker for osteoarthritis (OA). Our previous study revealed that the serum COMP level can be used to detect early cartilage change in non-OA patients with anterior cruciate ligament (ACL)-deficiency. However, there are still no studies on detecting the progression of cartilage degeneration in early OA. The aim of present study was to investigate whether serum COMP can detect the progression of cartilage degeneration after ACL reconstruction in non-OA patients. MethodsPatients without cartilage degeneration of early OA at ACL reconstruction and whose serum COMP levels could be measured were included in the study. Cartilage degeneration of early OA were defined as International Cartilage Repair Society (ICRS) grade 1 to 4 in more than 2 compartments or ICRS grade 2 to 4 in 1 compartment. The patients were divided into two groups: those who had cartilage degeneration of early OA at second-look arthroscopy (cartilage degeneration progression group) and those who did not (non-progression group), and the serum COMP values between the two groups were compared. ResultsThirty-one patients were included. There were 8 cases (25.8 %) in progression group and 23 cases (74.2 %) in non-progression group. There were significant differences between the two groups regarding age and change in serum COMP level. In terms of the rate of change in COMP, an increase of more than 1.24-fold was the cut-off value for detecting the progression of cartilage degeneration. ConclusionsIn this study, the increase in serum COMP levels was significantly greater in progressed cartilage degeneration group than non-progression group after ACL reconstruction. Longitudinal serum COMP measurement could detect the progression of cartilage degeneration. Level of evidenceLevel Ⅲ, retrospective comparative study.

Poster 218: Localized Acetabular Bone Density Distributions Are Altered in Unilateral Femoral Acetabular Impingement

Objectives: Femoral acetabular impingement (FAI) can lead to bony and cartilage changes at the joint, and it has been suggested that changes in bone mineral density in the acetabulum may correlate with osteoarthritic degeneration of the hip. In this study, we aimed to use opportunistic quantitative computed tomography (QCT) to map density distributions across the acetabular region in patients with unilateral FAI and determine if there were differences between the affected and unaffected side. Furthermore, we assessed if these differences in density distributions were associated with radiographic measures of FAI. Methods: Twenty patients (age 31.9 (SD 9.2), 13 female) who underwent surgery for unilateral FAI and had an associated CT scan of both hips were included in this retrospective study. Both sides of the pelvis were segmented, and 3D models were created. Estimated bone density values were mapped across the bone models via QCT. A thin-spline semi-landmarking approach was used to allow density values at equivalent anatomical points to be compared within patients and across the group. With the contralateral side used as the control, differences in bone density between sides were calculated. A mixed effect linear regression model was used to determine if there were associations between the localized bone density and radiographic measures of Tonnis grade, alpha angle, lateral center edge angle (LCEA), and cross over sign, while controlling for age and sex. To visualize the data, density changes and statistical results were color-mapped to the bone models. Results: Overall, several regions of the acetabulum were found to have increased bone density in the affected side compared to the contralateral (Figure 1). Specifically, the anterior-superior parts of the acetabular rim appeared to be most affected, along with the posterosuperior region (Figure 2). Limited associations were found between localized density and the clinical variables, with the most notable finding being a region of the superior rim that was found to be associated with the alpha angle (Figure 3). Conclusions: FAI leads to distinct patterns of bone density changes around the acetabulum, although there is still variability at the level of the individual patient. It is unclear whether these changes in bone density may be related to the underlying condition, alterations in the patient’s mechanics due to pain, or a combination of these factors. Providing detailed density maps of the bony anatomy may also assist surgical providers in planning interventions. Further research may elucidate the relationship between bone density changes and long-term degeneration of the joint.

The Implications of Brain-Derived Neurotrophic Factor in the Biological Activities of Platelet-Rich Plasma.

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity.

Intra-articular administration of extra-virgin olive oil in degenerative osteoarthritis

BackgroundWe aimed to analyze the outcomes of intraarticular extra virgin olive oil (EVOO) injection on mechanically induced rabbit knee osteoarthritis (OA) by studying the morphological, histological, and radiological findings.MethodsThe study was conducted on 32 New Zealand White rabbits. The randomly numbered subjects were divided into two main groups. The rabbits numbered 1 to 16 were selected to be the group to receive EVOO, and the remaining were selected into a control group. Both groups were separated into two subgroups for short-term (five weeks) and long-term (10 weeks) follow-up. Anterior cruciate ligament transection was applied on the left knees of all the rabbits via medial parapatellar arthrotomy to simulate knee instability. Immediately after the surgical procedure, 0.2 cc of EVOO was injected into the knee joint of rabbits numbered 1–16, and the control group received 0.2 cc of sterile saline. On the 14th day, long-term group subjects were administered another dose of 0.2 cc EVOO intraarticularly.ResultsThe gross morphological scores of the control group subjects were significantly different from the EVOO group for both short-term (p = 0,055) and long-term (p = 0,041) scores. In parallel, the MRI results of the EVOO subjects were significantly different from the control group for both short-term and long-term follow-up assessment scores (p = 0.017, p = 0.014, respectively). The Mankin scoring results showed that there were statistically significant differences between the EVOO and control group in the comparison of both total scores (p = 0.001 for short-term and p = 0.004 for long-term) and subgroup scoring, including macroscopic appearance, chondrocyte cell number, staining, and Tidemark integrity in both short-term (p = 0.005, p = 0.028, p = 0.001, p = 0.005, respectively) and long-term assessments (p = 0.002, p = 0.014, p < 0.001, p = 0. 200, respectively).ConclusionsWe have observed promising outcomes of intra-articular application of extra virgin olive oil in the treatment of acute degenerative osteoarthritis in rabbit knees. Due to its potential cartilage restorative and regenerative effects, EVOO, when administered intra-articularly, may be a promising agent to consider for further research in the treatment of OA.

Role of Autologous Micro-Fragmented Adipose Tissue in Osteoarthritis Treatment.

Osteoarthritis (OA) is the most common complex musculoskeletal disorder, resulting from the degeneration of the articular cartilage and characterized by joint pain and dysfunction that culminate in progressive articular cartilage loss. We present our experience in the management of hip and knee OA by means of the intra-articular injection of fat micrograft, describing our approach, which was developed from the belief in the powerful reparative effect of autologous fat graft on damaged tissue, as well as its natural lubricating effect on the joints. Inclusion criteria were as follows: men and women, aged 20 to 80 years, that referred articular pain of the hips and/or knees, showing initial-stage degenerative OA. From October 2018 to July 2023, a total of 250 patients underwent treatment with the Sefficare® device (SEFFILINE srl, Bologna, Italy). The Superficial Enhanced Fluid Fat Injection device was used to perform autologous regenerative treatments in a safe, standardized, easy, and effective way on 160 women, 64%, and 90 men, 36%. A total of 190 procedures (76%) involved the knees, with 20 patients who were bilaterally treated, while 60 procedures, all unilateral, involved the hips (24%). The mean age at treatment was 52.4 years. Before treatment, each patient had undergone X-rays and Magnetic Resonance Imaging (MRI) of the painful hip/knee to evaluate and grade the articular OA. Postoperatively, each patient was assessed after one, three, six, and twelve months. The donor site postoperative course was uneventful other than minimal discomfort. Clinically, the ROM (range of motion) of the treated knee/hip increased an average of 10 degrees 3 months after treatment, but the stiffness was reduced, as reported by the patients. The VAS (Visual Analog Scale) was submitted at 3, 6, and 12 months, demonstrating a progressive reduction of pain, with the best score obtained at six months postoperatively. In total, 85% of patients were satisfied one year after treatment, with a considerable improvement in pain and quality of life. The satisfactory outcome of this minimally invasive procedure indicates that the intra-articular injection of fat micrograft can replace or considerably delay the need for the classical major joint replacement surgery, thanks to its impact on the quality of life of patients and financial cost.

Beyond weakness: Exploring intramuscular fat and quadriceps atrophy in ACLR recovery.

Muscle weakness following anterior cruciate ligament reconstruction (ACLR) increases the risk of posttraumatic osteoarthritis (OA). However, focusing solely on muscle weakness overlooks other aspects like muscle composition, which could hinder strength recovery. Intramuscular fat is a non-contractile element linked to joint degeneration in idiopathic OA, but its role post-ACLR has not been thoroughly investigated. To bridge this gap, we aimed to characterize quadriceps volume and intramuscular fat in participants with ACLR (male/female = 15/9, age = 22.8 ± 3.6 years, body mass index [BMI] = 23.2 ± 1.9, time since surgery = 3.3 ± 0.9 years) and in controls (male/female = 14/10, age = 22.0 ± 3.1 years, BMI = 23.3 ± 2.6) while also exploring the associations between intramuscular fat and muscle volume with isometric strength. Linear mixed effects models assessed (I) muscle volume, (II) intramuscular fat, and (III) strength between limbs (ACLR vs. contralateral vs. control). Regression analyses were run to determine if intramuscular fat or volume were associated with quadriceps strength. The ACLR limb was 8%-11% smaller than the contralateral limb (p < 0.05). No between-limb differences in intramuscular fat were observed (p = 0.091-0.997). Muscle volume but not intramuscular fat was associated with strength in the ACLR and control limbs (p < 0.001-0.002). We demonstrate that intramuscular fat does not appear to be an additional source of quadriceps dysfunction following ACLR and that muscle size only explains some of the variance in muscle strength.

Management of Meniscus Pathology with Concomitant Anterior Cruciate Ligament Injury.

The purpose of this review is to summarize current clinical knowledge on the prevalence and types of meniscus pathology seen with concomitant anterior cruciate ligament (ACL) injury, as well as surgical techniques, clinical outcomes, and rehabilitation following operative management of these pathologies. Meniscus pathology with concomitant ACL injury is relatively common, with reports of meniscus pathology identified in 21-64% of operative ACL injuries. These concomitant injuries have been associated with increased age and body mass index. Lateral meniscus pathology is more common in acute ACL injury, while medial meniscus pathology is more typical in chronic ACL deficiency. Meniscus tear patterns associated with concomitant ACL injury include meniscus root tears, lateral meniscus oblique radial tears of the posterior horn (14%), and ramp lesions of the medial meniscus (8-24%). These meniscal pathologies with concomitant ACL injury are associated with increased rotational laxity and meniscal extrusion. There is a paucity of comparative studies to determine the optimal meniscus repair technique, as well as rehabilitation protocol, depending on specific tear pattern, location, and ACL reconstruction technique. There has been a substantial increase in recent publications demonstrating the importance of meniscus repair at the time of ACL repair or reconstruction to restore knee biomechanics and reduce the risk of progressive osteoarthritic degeneration. Through these studies, there has been a growing understanding of the meniscus tear patterns commonly identified or nearly missed during ACL reconstruction. Surgical management of meniscal pathology with concomitant ACL injury implements the same principles as utilized in the setting of isolated meniscus repair alone: anatomic reduction, biologic preparation and augmentation, and circumferential compression. Advances in repair techniques have demonstrated promising clinical outcomes, and the ability to restore and preserve the meniscus in pathologies previously deemed irreparable. Further research to determine the optimal surgical technique for specific tear patterns, as well as rehabilitation protocols for meniscus pathology with concomitant ACL injury, is warranted.

The Zitelli bilobed flap for soft tissue coverage after mucoid cyst resection: a retrospective cohort study

Purpose: Digital mucoid cysts are frequently found at the distal interphalangeal (DIP) joint in patients with degenerative osteoarthritis. In complicated cases, surgical treatment with mucoid cyst resection is considered, and soft tissue is covered with one of various local flap techniques. Among these, bilobed flaps are reliable and aesthetically favorable, with primary healing of the donor site. In this study, we investigated a case series of bilobed flaps for digital mucoid cysts.Methods: We retrospectively reviewed our electronic medical records and found 26 digital mucoid cysts treated with bilobed flaps at our facility between July 2022 and February 2024. We extracted data from the records of these patients on sex; age; time to surgery; clinical findings including nail ridging, the presence of osteophytes, cyst size and location, and additional procedures (arthrodesis); and follow-up data including the occurrence of complications, such as delayed wound healing, infection, stiffness, and recurrence.Results: Among the 26 patients in our sample, 19 were female and seven were male. The average age was 62.2 years, and the average time to surgery was 10.8 months. Preoperatively, the average cyst measured 6.9×8.3 mm. Nail ridging was found in 19 patients (73.1%) and osteophytes in 22 patients (84.6%). The most commonly affected digit was the middle finger, which accounted for 10 cases (38.5%). All the flaps totally survived, without major complications.Conclusion: Based on our series, a bilobed flap for soft tissue coverage after mucoid cyst excision can achieve high-quality surgical results.

Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice

BackgroundExtracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA.Materials and methodsTo determine whether Dspp+/– mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/–, and Dspp homozygous (Dspp−/−) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/– mice over time, condyles of Dspp+/– and WT mice were analyzed radiologically, histologically, and immunohistochemically.ResultsMicro-CT and histomorphometric analyses revealed that Dspp+/– and Dspp−/− mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp−/− mice which exhibited tooth loss, Dspp+/– mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/– mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/– mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage.ConclusionsDspp+/– mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

Early experience with the use of Cissus quadrangularis and Dalbergia sissoo therapy on bone marrow edema and knee pain associated with degenerative medial compartment knee osteoarthritis

Background: Bone marrow edema (BME) refers to the accumulation of excess fluid in the bone marrow, often indicative of injury or inflammation. Some studies suggest that incorporating plant-based therapies, rich in anti-inflammatory compounds and nutrients, may contribute to alleviating BME and promoting overall bone health. Aims and Objective: The study aims to evaluate the effect of Cissus quadrangularis and Dalbergia sissoo therapy on BME and knee pain associated with degenerative medial compartment knee osteoarthritis (OA). Materials and Methods: This retrospective study examined seven individuals with medial tibial condyle BME associated with medial compartment OA. These patients were treated with initial 10 days of non-steroidal anti-inflammatory drugs along with once-a-day tablet containing C. quadrangularis (500 mg) and D. sissoo (400 mg). Visual analogue scores (VAS) and Oxford knee score (OKS) were noted at the beginning of the therapy and at 12 weeks of completion of therapy. Before treatment, BME (percentage of the medial tibial condyle) and presence/absence of subtle subchondral fracture were diagnosed with T2-weighted magnetic resonance imaging (MRI) images, and subsequently, its resolution was confirmed with a repeat MRI scan at 12 weeks. Results: At the end of 12 weeks of therapy, there was a statistically significant improvement in the mean VAS score (baseline 8.14±0.90 improved to 2.00±0.58 at 12 weeks, [P&lt;0.0001]), OKS (baseline 25.71±1.80 improved to 36.57±1.51 at 12 weeks, [P=0.0001]), and there was statistically significant decrease in mean BME (baseline 37.86±10.35% decreased to 14.29±4.50% at the end of 12 weeks, [P=0.0001]). Conclusion: Our early experience shows that the combination therapy of C. quadrangularis + D. sissoo is effective in relief of pain, improvement in knee function, and resolution of BME associated with medial compartment knee OA. This combination is safe, effective, and well-tolerated by patients’ population.

Cartilage stem/progenitor cells-derived exosomes facilitate knee cartilage repair in a subacute osteoarthritis rat model.

Cartilage defects in the knee are often associated with the progression of degenerative osteoarthritis (OA), and cartilage repair is a useful strategy for managing this disease. However, cartilage repair is challenging because of the unique environment within the tissue. Recently, stem cell-based therapies have shed new light on this issue. In this study, we prepared exosomes (EXOs) from cartilage stem/progenitor cells (CSPCs) and found that treatment with EXOs increased the viability, migration, and proliferation of cultured primary chondrocytes. In a subacute OA rat model, the application of EXOs facilitated cartilage regeneration as evidenced by histological staining. Exosomal protein analysis together with bioinformatics suggested that cyclin-dependent kinase 9 (CDK9) is a key factor for chondrocyte growth and migration. Functional studies confirmed this prediction, that is, inhibiting CDK9 reduced the beneficial effects induced by EXOs in primary chondrocytes; while overexpression of CDK9 recapitulated the EXOs-induced phenotypes. RNA-Seq data showed that a set of genes involved in cell growth and migration were up-regulated by EXOs in chondrocytes. These changes could be partially reproduced by CDK9 overexpression. Overall, our data suggest that EXOs derived from primary CSPCs hold great therapeutic potential for treating cartilage defect-associated disorders such as degenerative OA, and that CDK9 is a key factor in this process.

Mechanism of acupoint penetration acupuncture therapy regulating chondrocyte autophagy via the PI3K/Akt-mTOR pathway in KOA rats

ObjectiveTo investigate whether acupoint penetration acupuncture (APA) could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis (KOA) rats. MethodsKOA was induced in rats via intra-articular injection of sodium iodoacetate resolution. Forty male Sprague-Dawley rats were randomly assigned to blank control, model, APA, electro-acupuncture (EA), and sham model groups (n = 8) and those in the APA and EA groups received their respective therapies. Following completion of the treatment course, histological examinations of cartilage and muscle were conducted. Levels of apoptosis- and autophagy-related factors, including Bax, Bcl-2, mTOR, ULK-1, and Beclin-1 protein, and mRNAs were assessed. Additionally, β-endorphin (β-EP) concentrations in the brain and serum were measured. ResultsHistological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group. APA inhibited cartilage degeneration by modulating the expression of apoptosis- and autophagy-related proteins and mRNA, thus preventing chondrocyte apoptosis. In the APA group, Bax and mTOR protein levels were significantly lower than those in the model group (both P = .024). Conversely, the Bcl-2 expression level was significantly higher than that in the EA group (P = .035). Additionally, ULK-1 expression was significantly lower than that in the EA group (P = .045). The mRNA level of Bax was significantly higher than that in the blank control group (P < .001). However, Beclin-1 levels were significantly higher than those in both the model and EA groups (both P < .001). ELISA results showed a significant decrease in the concentration of β-EP in the brains of the rats in the APA group compared with those in the model group (P = .032). ConclusionsAPA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.

Mechanism of Tougu Xiaotong Capsules in delaying degeneration of osteoarthritis by regulating cholesterol metabolism in chondrocytes through lncRNA MALAT1

From the perspective of lncRNA MALAT1 regulating cholesterol metabolism in chondrocytes, this paper explores the effect and mechanism of Tougu Xiaotong Capsules(TGXTC) in delaying the degeneration of osteoarthritis. After one week of adaptive feeding, 48(8-week-old) C57BL/6 mice were randomly divided into a blank group(12 mice) and a model group(36 mice) by random number table method. The mice in the model group were anesthetized by inhalation of 5% isoflurane, and the OA model was induced by Hulth method. The experiment randomly divided the mice into a model group(12 mice), a drug-positive group(taururso-deoxycholic acid)(12 mice), and a TGXTC group(12 mice). The drug-positive group was given 500 mg·kg~(-1) taurodeoxycholic acid by intragastric administration. TGXTC group was given TGXTC 368 mg·kg~(-1) by gavage. The blank group and model group were given the same amount of normal saline for four weeks. After the intervention, the mice in each group were killed under anesthesia, and the knee cartilage tissue was separated and collected. The morphologic changes of knee cartilage were observed. The level of lncRNA MALAT1 in the cartilage tissue was detected by real-time PCR. The protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in mouse articular cartilage were detected by Western blot. Lentivirus-coated plasmid was used to transfect mouse chondrocytes with sh-MALAT1. The gene levels of lncRNA MALAT1 in mouse chondrocytes transfected with sh-MALAT1 were detected by real-time PCR. Western blot was used to detect the effect of TGXTC on the protein content of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in thapsigargin(TG)-induced mouse chondrocytes after lncRNA MALAT1 knockdown. Flow cytometry was used to detect the effect of TGXTC on apoptosis of TG-induced mouse chondrocytes after lncRNA MALAT1 knockdown. The results of HE and saffranine O staining showed that compared with the model group, the structure of the cartilage layer was basically intact; the damage degree of joint structure was significantly improved, and the cartilage matrix was significantly enhanced by saffranine O staining in the TGXTC group and drug-positive group. Compared with the model group, the lncRNA MALAT1 level was significantly decreased in the TGXTC group and drug-positive group. Compared with the model group, the protein content of ABCA1, ApoA1, and LXRβ was significantly increased, while that of CHOP and caspase-3 in the TGXTC group and drug-positive group significantly decreased. Compared with the TG group, the lncRNA MALAT1 level in the TG+sh-MALAT1 group was decreased. The lncRNA MALAT1 level in the TG+sh-MA-LAT1+TGXTC group was increased compared with the TG+TGXTC group. Western blot results showed that compared with the model group, protein expressions of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in the TGXTC group were significantly decreased, after lncRNA MALAT1 knockdown, the regulation and apoptosis of ABCA1, ApoA1, LXRβ, CHOP, and caspase-3 in TG-induced mouse chondrocytes were weakened by TGXTC. TGXTC can improve the disorder of cholesterol metabolism in OA chondrocytes and delay OA degeneration, which is closely related to the regulation of lncRNA MALAT1.

Effects of Accelerated Rehabilitation Exercise on the Senior Fitness Test (SFT), Isometric Muscle strength, and Blood Profile in Older Adult Women with Degenerative Knee Osteoarthritis

PURPOSE This study aimed to investigate the effects of accelerated rehabilitation exercise on physical fitness, lower extremity isometric strength, and blood variables in older adult women diagnosed with degenerative osteoarthritis.METHODS A total of 29 older adult women diagnosed with degenerative osteoarthritis residing in G city participated in the study, and 19 participants, excluding dropouts, took part in the experiment. They underwent exercise twice a week for 60 minutes per session over a period of 12 weeks. Pre- and post-experiment, the older adult fitness assessment (SFT), lower extremity isometric strength, and blood variables were measured. Data analysis was performed using SPSS 25.0, and paired sample t-tests were conducted to examine the effects before and after exercise.RESULTS The study results showed significant differences in body mass index (BMI) before and after exercise (p&lt;0.05), and the older adult fitness assessment (SFT) showed significant differences in all items (p&lt;0.01). Lower extremity isometric strength showed significant differences in absolute (Nm) and relative (%BW) values of 20° right flexion muscle (p&lt;0.01). In terms of blood variables, significant differences were observed in creatine and ESR before and after exercise (p&lt;0.01).CONCLUSIONS This study’s results suggest that regular physical activity and rehabilitation exercise programs can positively impact the muscular strength, cardiovascular endurance, exercise function, and blood composition of older adult women diagnosed with degenerative osteoarthritis. It is indicated that conducting future research, including periodic exercise programs, could be beneficial in promoting sustained exercise participation.

A Case of Baker’s Cyst with Synovial Chondromatosis of Knee

Synovial chondromatosis is a benign condition which arises from synovial membrane or bursae around the joints. Joint abnormalities in the form of arthritic or mechanical conditions such as detachment of osseocartilaginous fragments from the articular surface are its secondary associations. Rarely there maybe involvement of the Baker’s cyst. Here we report a case in which a 60-year-old female came with complaints of pain, swelling and restriction of movement of right knee joint for the past one year. After careful clinical and radiological examination, it was diagnosed as Baker’s cyst complicated by synovial chondromatosis. After the diagnosis the patient underwent the following procedures: open synovectomy, cyst removal and thorough joint debridement. Synovial chondromatosis was confirmed histopathologically. Secondary synovial chondromatosis has features of osteoarthritic changes, lack of extensive synovial proliferation and complicated Baker's cyst which is not seen in primary synovial chondromatosis.&#x0D; Synovial chondromatosis (SC) is caused by metaplasia of the synovium into chondrocytes and is a rare benign disorder.[1,2] Primary synovial chondromatosis (PSC) is a self-limited process that occurs in an otherwise normal joint.[3] When synovial chondromatosis develops in a joint previously affected with disease, often posttraumatic or degenerative osteoarthritis, it is called as secondary synovial chondromatosis.[4] SC may involve any joint, but the most common joint involved is knee joint followed by hip joint, and small joints of the hand and wrist. Least involvement is seen in elbow and shoulder joint. [5] The disease is categorised into three phases according to Milligram classification: active intrasynovial disease without any loose bodies observed in the early phase, active disease and loose bodies observed in the transitional phase, and multiple loose bodies without any intrasynovial disease observed in the late phase.&#x0D; In orthopaedic practice, popliteal cysts are common occurrence; many of them are associated with degenerative or rheumatoid arthritis. The differential diagnoses become more complex when loose bodies and calcifications are noted within the joint on a radiograph. Here in, we are presenting a case of Baker’s cyst with synovial chondromatosis of knee treated by surgical excision and confirmed by histopathology.

A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis.

Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral-biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)-based nanoparticles (NPs) are integrated into poly(D, L-lactide)-poly(ethylene glycol)-poly(D, L-lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self-assembled ChS and ε-poly-l-lysine (EPL) NPs are prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in interleukin-1β (IL-1β)-mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS-based hydrogel system offers a potential strategy to regulate the chondrocyte-macrophage crosstalk, thus re-establishing the anti-inflammatory and immunomodulatory microenvironment for OA therapy.

Inhibition of the MALT1-LPCAT3 axis protects cartilage degeneration and osteoarthritis

The proinflammatory cytokines and arachidonic acid (AA)-derived eicosanoids play a key role in cartilage degeneration in osteoarthritis (OA). The lysophosphatidylcholine acyltransferase 3 (LPCAT3) preferentially incorporates AA into the membranes. Our recent studies showed that MALT1 [mucosa-associated lymphoid tissue lymphoma translocation protein 1]) plays a crucial role in propagating inflammatory signaling triggered by IL-1β and other inflammatory mediators in endothelial cells. The present study shows that LPCAT3 expression was up-regulated in both human and mice articular cartilage of OA, and correlated with severity of OA. The IL-1β-induces cell death via upregulation of LPCAT3, MMP3, ADAMTS5, and eicosanoids via MALT1. Gene silencing or pharmacological inhibition of LPCAT3 or MALT1 in chondrocytes and human cartilage explants notably suppressed the IL-1β-induced cartilage catabolism through inhibition of expression of MMP3, ADAMTS5, and also secretion of cytokines and eicosanoids. Mechanistically, overexpression of MALT1 in chondrocytes significantly upregulated the expression of LPCAT3 along with MMP3 and ADAMTS5 via c-Myc. Inhibition of c-Myc suppressed the IL-1β-MALT1-dependent upregulation of LPCAT3, MMP3 and ADAMTS5. Consistent with the in vitro data, pharmacological inhibition of MALT1 or gene silencing of LPCAT3 using siRNA-lipid nanoparticles suppressed the synovial articular cartilage erosion, pro-inflammatory cytokines, and eicosanoids such as PGE2, LTB4, and attenuated osteoarthritis induced by the destabilization of the medial meniscus in mice. Overall, our data reveal a previously unrecognized role of the MALT1-LPCAT3 axis in osteoarthritis. Targeting the MALT1-LPCAT3 pathway with MALT1 inhibitors or siRNA-liposomes of LPCAT3 may become an effective strategy to treat OA by suppressing eicosanoids, matrix-degrading enzymes, and proinflammatory cytokines.Graphical

Is Osteoarthritis a Vascular Disease?

Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The pathophysiology strongly implicates intricate chemical communication, primarily through cytokines, leading to the production of degradative enzymes in cartilage, inflammatory peptides in synovium, and structural changes in bone, resulting in characteristic clinical features such as joint deformities and loss of cartilage space seen on X-rays. Recent studies highlight the previously underestimated role of subchondral bone in OA, revealing its permeability to cytokines and raising questions about the influence of abnormal perfusion on OA pathophysiology, suggesting a vascular component in the disease's etiology. In essence, alterations in bone perfusion, including reduced venous outflow and intraosseous hypertension, play a crucial role in influencing the physicochemical environment of subchondral bone, impacting osteoblast cytokine expression and contributing to trabecular remodeling, changes in chondrocyte phenotype, and ultimately cartilage matrix degeneration in OA. Dynamic contrast (gadolinium) enhanced magnetic resonance imaging (DCE-MRI) was used to quantify perfusion kinetics in normal and osteoarthritic subchondral bone, demonstrating that decreased perfusion temporally precedes and spatially correlates with cartilage lesions in both young Dunkin-Hartley (D-H) guinea pigs and humans with osteoarthritis. Pharmacokinetic analysis of DCE-MRI generated data reveals decreased tracer clearance and outflow obstruction in the medial tibial plateau of osteoarthritic guinea pigs, coinciding with progressive cartilage degradation, loss of Safranin O staining, and increased expression of matrix metalloproteinases and interleukin-1. Positron emission tomographic (PET) scanning using 18F-Fluoride reveals a relationship among bone blood flow, cartilage lesions, and 18F-Fluoride influx rate in OA, highlighting the intricate relationships between decreased perfusion, altered bone metabolism, and the progression of osteoarthritis. These findings, supported by 18F-Fluoride PET data, suggest the presence of venous stasis associated with outflow obstruction, emphasizing the role of decreased subchondral bone perfusion in the pathophysiology of OA and its association with reduced osteoblast activity and advanced cartilage degeneration.