Degenerative Osteoarthritis Research Articles

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Return to Sports Activity After Reverse Total Shoulder Arthroplasty.

There are little published data on return to sports (RTS) after reverse total shoulder arthroplasty (RTSA). To (1) determine the rate and timing of RTS after RTSA in an Asian population, (2) analyze predictive factors for RTS, and (3) determine the relationship between RTS after RTSA and clinical/radiological outcomes. Case-control study; Level of evidence, 3. A retrospective review was performed on consecutive patients with diagnosis of irreparable rotator cuff tear (RCT), cuff tear arthropathy (CTA), or degenerative osteoarthritis who underwent RTSA between May 2017 and May 2020. Included were patients who played sports preoperatively in ≤3 years and had ≥2-year follow-up. Patients were divided into 2 groups based on responses to a telephone survey about RTS after RTSA: those who returned to sports (group A) and those who did not (group B). Patient characteristics, pre- and postoperative clinical features and functional scores, and radiologic outcomes (acromial fracture, scapular notching, heterotopic ossification, and loosening of humeral and glenoid component) were compared between the groups. Of 59 eligible patients, 44 patients (28 in group A, 16 in group B) were included. The RTS rate after RTSA was 63.6%, and the mean RTS time was 9.1 months (range, 3-36 months). There was a significant group difference in body mass index (BMI) (group A, 24.3 ± 2.1; group B, 27.1 ± 4.4; P = .01) and preoperative diagnosis (CTA/irreparable RCT/degenerative osteoarthritis diagnoses: group A, 13/12/3; group B, 3/6/7; P = .03). Patients in group A showed significantly higher forward flexion (P = .03) and higher Simple Shoulder Test score (P = .02) than group B at final clinical follow-up. No significant difference in radiological outcomes was found between the groups. Patients with a low BMI and those diagnosed with CTA or irreparable RCT were found to have better RTS rates after undergoing RTSA, and forward flexion and Simple Shoulder Test scores at final follow-up were significantly higher in the RTS group, with no significant differences in complications.

Ultra-Short Echo Time-MRI T2* Mapping of Articular Cartilage Layers Is Associated with Histological Early Degeneration.

Ultra-short TE (UTE) sequences on MRI are a technique that improves the visualization of tissues with short T2 relaxation time, such as deep cartilage layers. In addition, T2* relaxation time calculated from the UTE has the potential to evaluate water molecules bound to the cartilage matrix. This study was performed to determine if there is an association between UTE-T2* relaxation time by cartilage layer and histological degeneration in knee osteoarthritis (OA). Seven knees that had undergone total knee arthroplasty (TKA) were included in the study, and the lateral tibial cartilage, which had the least degeneration of the resected bones, was used as the sample. The T2* relaxation time of 4 patients with no abnormal findings on MRI was the reference relaxation time. Histological degeneration of TKA samples was assessed by the Mankin score and graded as the early OA group (≤3 points) and the advanced OA group (≥4 points). The association between T2* relaxation time and Mankin grade in each cartilage layer was compared. The effect of angiogenesis to the tidemark on T2* relaxation time was also compared. T2* relaxation time of the cartilage layer was significantly longer in early OA than that in the control group. In the deep cartilage layer, the mean T2* relaxation time for angiogenesis (-) was 15.7 ms, whereas it was significantly shorter for angiogenesis (+) at 8.2 ms. The UTE-T2* relaxation time was associated with histological cartilage degeneration, suggesting a potential application in monitoring early cartilage degeneration.

FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis

Osteoarthritis (OA) is the most common joint disease, but no disease-modifying drugs have been approved for OA treatment. Mitophagy participates in mitochondrial homeostasis regulation by selectively clearing dysfunctional mitochondria, which might contribute to cartilage degeneration in OA. Here, we provide evidence of impaired mitophagy in OA chondrocytes, which exacerbates chondrocyte degeneration. Among the several classic mitophagy-regulating pathways and receptors, we found that FUNDC1 plays a key role in preserving chondrocyte homeostasis by inducing mitophagy. FUNDC1 knockdown invitro and knockout invivo decreased mitophagy and exacerbated mitochondrial dysfunction, exacerbating chondrocyte degeneration and OA progression. FUNDC1 overexpression via intra-articular injection of adeno-associated virus alleviated cartilage degeneration in OA. Mechanistically, our study demonstrated that PFKP interacts with and dephosphorylates FUNDC1 to induce mitophagy in chondrocytes. Further analysis identified KD025 as a candidate drug forrestoring chondrocyte mitophagy by increasing the FUNDC1-PFKP interaction and thus alleviating cartilage degeneration in mice with DMM-induced OA. Our study highlights the role of the FUNDC1-PFKP interaction in chondrocyte homeostasis via mitophagy induction and identifies KD025 as a promising agent for treating OA by increasing chondrocyte mitophagy.

IL-17 in osteoarthritis: A narrative review.

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

Hallux Valgus: The Influence of Intersesamoid Crista's Osteoarthritis on Frontal Plane Pronation

A frontal plane metatarsal rotational (pronation) has been documented in a high percentage of hallux valgus patients. Pathoanatomical concepts leading to pronation are still debated. Nevertheless, there is no consensus on how to measure this component of the deformity. The aim of the present study was to find potential associations between sesamoid's crista osteoarthritis and the frontal plane deformity in HV cases. Our study showed a moderate correlation between the crista's OA and the intermetatarsal angle (IMA), the hallux valgus angle (HVA) and the alpha angle. In severe hallux vulgus deformed specimens, with an eroded inter-sesamoid crista, frontal plane pronation was not as prevalent nor severe as in those without osteoarthritic degeneration. Severe hallux valgus cases with a completely eroded crista, showed lower pronation, and higher IMA, when compared to specimens with a preserved anatomy. This brings to light the inter-sesamoid crista's unique function in retaining the IMA. Understanding the role the frontal plane plays in hallux valgus' biomechanics and in its radiographic appearance is vital to change the current paradigm.

Medial open-wedge high tibial osteotomy for the treatment of degenerative varus knee osteoarthritis in geriatric patients: a retrospective study

HTO has proven to be a cost-effective surgical procedure in the treatment of KOA, but few investigations have studied radiological changes and clinical effectiveness of OWHTO in geriatric patients. 76 patients were recruited in this retrospective study. According to the age, patients were divided into two groups (≤ 60, Group “Young”; > 60, Group “Geriatric”). Demographic data, radiological imaging and postoperative complications were analyzed. Kellgren–Lawrence grade (K–L), weight-bearing line ratio (WBLR); posterior tibial slope angle (PTS); American knee score (AKS); Western Ontario and McMaster Universities Arthritis Index (WOMAC) and visual analog scale (VAS) were introduced to estimate the clinical outcome of OWHTO. There were 18 male and 58 female patients in the present study with a mean age of 58.5 ± 9.2 years (ranges from 40 to 82 years); the average age was 51.4 ± 4.1 years and 67.3 ± 4.9 years for group Y and G respectively, 44.7% and 31.5% patients were older than 60 and 65 years. BMI for the 76 patients was 26.6 ± 3.2 kg/m2, and geriatric patients were more likely accompanied by one or more comorbidities (70.6 vs. 45.2%). There were 34 and 42 patients in group Geriatric and group Young respectively, and no significant difference of MPTA, WBLR, PTS and WOMAC, VAS, AKS and ROM between the two group (P > 0.05) were found. After more than a two-year follow-up period, postoperative WBLR, AKS, WOMAC and VAS were much more desired than preoperative, and no significant difference of these variables between the young and geriatric group (P > 0.05), however, elderly patients were more likely to suffer from a longer bone union time. OWHTO can avoid geriatric patients from undergoing secondary knee surgery in the short term, however the survival rate of OWHTO in geriatric patients should be ultimately clarified by different studies.

Association Between Osteoarthritis Burden and Intervertebral Disk Degeneration in Patients Undergoing Lumbar Spine Surgery for Degenerative Lumbar Spondylolisthesis.

A retrospective analysis of prospectively collected data. To assess the association between intervertebral disk degeneration and hip and knee osteoarthritis (OA) in patients with degenerative lumbar spondylolisthesis. The co-occurrence of hip OA and degenerative spinal pathologies was first described as the "hip-spine syndrome" and has also been observed in knee OA. It remains unclear whether both pathologies share an underlying connection beyond demographic factors. Intervertebral disk degeneration was classified by the Pfirrmann Classification and intervertebral vacuum phenomenon. Intervertebral vacuum phenomenon was classified into mild (1 point), moderate (2 points), and severe (3 points) at each level and combined into a lumbar vacuum score (0-15 points). Similarly, a lumbar Pfirrmann grade was calculated (5-25 points). Patients with previous hip or knee replacement surgery were classified as having an OA burden. We used multivariable regression to assess the association between OA and disk degeneration, adjusted for age, body mass index, and sex. A total of 246 patients (58.9% female) were included in the final analysis. Of these, 22.3% had OA burden. The multivariable linear regression showed an independent association between OA burden and lumbar vacuum (β = 2.1, P <0.001) and Pfirrmann grade (β = 2.6, P <0.001). Representing a 2.1 points higher lumbar vacuum and 2.6 points higher lumbar Pfirrmann grade after accounting for demographic differences. Our study showed that OA burden was independently associated with the severity of the intervertebral disk degeneration of the lumbar spine. These findings give further weight to a shared pathology of OA of large joints and degenerative processes of the lumbar spine. 3.

Correlation Between Synovial Fluid Levels of Matrix Metalloproteinase's (MMP-1, MMP-3, and MMP-9) and TNF-α with the Severity of Osteoarthritis Knee in Rural Indian Population.

In India, 22% to 39% of the ageing population suffers from degenerative knee osteoarthritis (OA), making it the most prevalent joint disorder in the knee. MMP-1, MMP-3, and MMP-9 protein expression levels have all been associated with OA. The aim of the present study was to establish a relationship between synovial fluid levels of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and tumour necrosis factor-alpha (TNF-α) with different Kellgren-Lawrence Grading scale as per the severity of knee osteoarthritis (OA). This hospital-based observational study included 87 individuals with knee osteoarthritis examined at the orthopaedics department outpatient clinic at the tertiary care teaching hospital in rural area of north India. In-person interviews were conducted to gather data, through a semi-structured, pretested interview schedule. To determine the degree and severity of OA, the levels of the enzymes matrix metalloproteinase MMP-1, MMP-3, and MMP-9 as well as tumour necrosis factor (TNF-α) were assessed in the synovial fluid of knee of each study participant. The levels of MMP-1, MMP-3, MMP-9, and TNF-α in synovial fluid were significantly correlated with the severity of osteoarthritis as determined by the Kellgren-Lawrence Grading Scale. Age, duration of symptoms and BMI showed a strong positive and significant correlation with biochemical markers (MMP-1, MMP-3, MMP-9, and TNF-α) in synovial fluid of Knee. Level of biochemical markers (MMP-1, -3, -9, and TNF-α) in synovial fluid act as diagnostic markers and have a positive correlation with the severity of osteoarthritis knee, age, weight/BMI and duration of disease. However, no significant correlation was found between the level of aforementioned biochemical markers with sex, height, inflammation of the knee, morning stiffness, and age of onset of disease.

Prosthesis Options for Proximal Interphalangeal Joint Arthroplasty in Osteoarthritis: A Systematic Review and Meta-Analysis.

Background: Literature investigating the long-term outcomes of prosthesis options for proximal interphalangeal (PIP) joint arthroplasty is scarce, with most reports combining indications and underlying pathologies in analyses. In this study, we aim to compare silicone, pyrocarbon and metal prostheses in PIP joint arthroplasty for primary degenerative osteoarthritis (OA). Methods: A review of scientific literature published between 1990 and 2021 was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant studies were screened and the appropriate data was extracted. An evaluation of clinical outcomes (range of motion [ROM] and pain), complications (reoperation) and survival rates for each prosthesis was performed. Results: Twelve studies were included for analysis with a total of 412 PIP joints. ROM was 66.6°, 55.8° and 46.4° for metal, silicone and pyrocarbon implants, respectively. Silicone implants had the best pain score on the visual analogue scale (1.2) followed by the pyrocarbon (2.6) and metal (3.9) groups. Complication rates were lowest in silicone implants (11.3%) compared to 18.5% in pyrocarbon and 22.4% in metal prostheses. Survival did not differ significantly amongst the three groups. Conclusions: Our findings suggest that for patients with primary degenerative OA, PIP joint arthroplasty using a silicone prosthesis can provide greater pain relief with lower complication rates compared to other implant options. Level of Evidence: Level III (Therapeutic).

Bone marrow aspirate concentrate – A novel approach to alter the course of temporomandibular joint osteoarthritis (a clinical study)

IntroductionTMJ OA is characterized by severe osteocartilaginous degradation of the joint structure resulting in severe deterioration of both joint function as well as joint structure. bone marrow aspirate concentrate (BMAC) gained wide acceptance as an auspicious addition for regenerative medicine as it is confirmed to be a rich source of pluripotent mesenchymal stem cells and growth factors that produce promising relief of clinical symptoms with significant repair of the joint structure. Thus, the study aims at assessing the efficacy of bone marrow aspirate concentrate (BMAC) as a treatment modality for TMJ osteoarthritis and compare its efficacy with that of hyaluronic acid (HA). Methods24 patients were included in the present study and divided into 12 patients in each group. Joint arthrocentesis was performed to all patients followed by intra-articular BMAC injection in Group I. While Group II received HA acid injection ResultsA trend towards long term joint repair at 12 and 18 months follow up period was observed in the bone marrow aspirate concentrate (BMAC) group as a therapeutic modality for TMJ OA by providing necessary growth factors and anti-inflammatories that impedes the progression of the osteoarthritic degeneration. On the contrary to the viscosupplementary action of hyaluronic acid (HA) that showed relapse of patients conditions. ConclusionBone marrow aspirate concentrate (BMAC) is able to reverse the degenerative effects of TMJ OA however,further studies are mandatory with larger population and longer follow-up time.

In vitro and in vivo investigations on arsenic-induced cartilage degeneration in osteoarthritis

Heavy metals found in the environment, including arsenic (As) pose significant risks to human health and present a risk factor for osteoarthritis (OA). This study researched the impact of As on cartilage degeneration by focusing on the role of As in causing OA in mice. We employed chemical inhibition and inductively coupled plasma mass spectrometry analyses to identify the effect of As on chondrocytes as well as studying its accumulation in organs after oral administration in mice. Additionally, the study examined the effect of intra-articular As treatment on the levels of crucial catabolic factors, namely Hif-2α (Epas1) and Zip8 (Slc39a8), during OA progression. Mice that were administered As orally in conjunction with surgically induced joint instability, had heightened cartilage destruction compared to wild-type mice. Quantitative analysis revealed a significant increase in Hif-2α and Zip8 mRNA expression (p = 0.0352,0.0004 respectively) and protein expression (p = 0.0101,0.008 respectively) post oral administration. Our findings illustrated the role of As in influencing crucial cellular functions that are triggered by reactive oxygen species. These events consequently activate the Akt/Hif-2α/NF-κB pathways, leading to disruptions in articular cartilage homeostasis. This study provides a comprehensive understanding of the impact of As on the development of osteoarthritis.

The Role of Matrix Metalloproteinase 13 and Vitamin D in Osteoarthritis: A Hospital-Based Observational Study.

Introduction Osteoarthritis (OA) is the most common form of degenerative joint disease characterized by the progressive degeneration of articular cartilage, osteophyte formation, and joint space narrowing. Matrix metalloproteinases (MMPs) are potential biomarkers for osteoarthritis. Aims and objective The study's aim is the estimation of serum and synovial fluid matrix metalloproteinase (MMP) 13 and serum vitamin D levels in the grade 3 and grade 4 stages of osteoarthritis according to the Kellgren and Lawrence (KL) system of classification. Materials and methods A total of 100 subjects were included; of them, 25 patients with grade 3 and 25 patients with grade 4 knee osteoarthritis diagnosed clinically and radiologically according to the Kellgren and Lawrence criteria have been enrolled in the study, and 50 patients with knee pain having a diagnosis other than degenerative OA of the knee were taken as controls. Venous blood and synovial fluid have been collected from all of them for the estimation of MMP-13 and vitamin D. The enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) methods were used for the estimation of MMP-13 and vitamin D, respectively. Results The mean value of synovial fluid MMP-13 was found to be elevated in grade 4 as compared to grade 3 and the control group, whereas the mean value of serum MMP-13 was found to be elevated in grade 3 as compared to grade 4 and control. The level of serum vitamin D was found deficient in OA patients as compared to control. The Kruskal-Wallis test was performed to compare these groups, and there was a significant difference between these groups(p-value of <0.05). Summary and conclusion High synovial and serum MMP-13 is associated with knee structural abnormalities in patients with knee OA as compared to the control groupsuggesting that MMP-13 can be a biomarker in knee OA, whereas the decreased level of vitamin D may be associated with an increased risk for the progression of OA; hence, serum vitamin D may be a good indicator for the prediction of the initiation of OA.

Clinical Outcome of Minimally Manipulated, Mechanically Isolated Autologous Adipose Tissue-Derived Stromal Vascular Fraction (Sahaj Therapy®) in Knee Osteoarthritis-Randomized Controlled Trial.

Regenerative therapy has shown promising results in the treatment of osteoarthritis (OA) knee with Kellgren-Lawrence (KL) Grades I-III. We compared the safety, efficacy, functional, and clinical outcomes of intra-articular implantation of autologous adipose tissue-derived stromal vascular fraction (SVF) isolated using direct ultrasonic cavitation (Sahaj therapy-Cell Innovation Patented Technology) and saline injection in knee osteoarthritis. The present prospective observational study was conducted over 3years. We enrolled 120 patients in our study, where four patients got excluded as they did not meet the inclusion criteria. The remaining 116 patients were randomized into two groups, one with autologous adipose tissue-derived SVF and the other group with saline injection. A comparison of mean KOOS and VAS scores at different follow-ups was done using Paired 't' test. A p value of < 0.05 was considered significant. The results show that the SVF group had significantly higher KOOS scores (78.49 ± 6.54 in the SVF group vs 59.19 ± 5.14 in the saline group), respectively (p < 0.001). Similarly, the SVF group had significantly lesser VAS scores (3.17 ± 0.94 in the SVF group vs 3.89 ± 1.04 in the saline group), respectively (p < 0.001). Autologous adipose tissue-derived SVF is a better choice for treating knee osteoarthritis. For individuals with degenerative osteoarthritis, autologous SVF grafting in the same surgical procedure is an innovative and promising treatment modality. Even after 3years of follow-up, the study participants with OA knee have shown a good clinical and functional outcome.

Quality of life in individuals with knee osteoarthritis versus asymptomatic individuals.

Osteoarthritis (OA) is characterised by joint degeneration and represents the leading cause of disability in old age. OA entails a personal burden, with suffering and reduced quality of life (QoL). To compare the QoL of individuals with OA to that of asymptomatic individuals in order to determine the actual impact of OA on the affected population. Cross-sectional study with a sample of 140 patients diagnosed with OA. Another 51 sex- and age-matched asymptomatic individuals with no clinical signs of knee OA or lower limb osteoarticular symptoms for at least the preceding six months were recruited. Knee OA was stratified radiologically according to the Ahlbäck classification (1968). QoL was measured using the SF-36 questionnaire (Medical Outcomes Study 36-Item Short-Form Health Survey). The participants were assigned to "osteoarthritis" (OG) or "asymptomatic" (AG) groups. The OG presented greater body mass and BMI than the AG. Perceived QoL was worse for the OG than the AG across SF-36 domains. In the comparison of the grades of OA degeneration, the group with Ahlbäck grades 4 and 5 (severe) perceived their QoL as poorer than those with grades 1, 2, and 3 (moderate). The grade of OA, older age, and BMI were shown to be strong independent predictors of poor perceived quality of life. Individuals with knee OA showed worse perceived QoL compared with asymptomatic individuals. The domains with the lowest scores were physical functioning and functional limitation. Quality of life was influenced by BMI, age, sex, and grade of osteoarthritis.

Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.

Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study. Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated. We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE. The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

Inflammation‐Regulated Auto Aggregated Hydrogel Microspheres Via Anchoring Cartilage Deep Matrix for Genes Delivery

AbstractThe high density structure of cartilage matrix negative charge seriously hinders the penetration and enrichment of drugs/genes into cartilage tissue. In this study, hexachlorocyclotriphosphonitrile is used as the core to prepare self‐polymerized phosphorus dendrimers with inflammatory reaction through substitution and condensation reaction. The vector can achieve efficient penetration of the damaged articular cartilage (slightly acidic condition) and effective anchoring of cartilage matrix (normal physiological condition) through the size effect under inflammatory response. Meanwhile, as a gene “delivery library,” G1‐NC5.HCl@siRNA is gradually released with microspheres degrading; the long‐term silencing of specific genes is realized. Further, G1‐NC5.HCl@siRNA is loaded into the hydrogel microspheres by ionic bond coordination and microfluidic techniques to improve the residency effect of G1‐NC5.HCl@siRNA in the joint cavity. The results of cartilage in vitro and in vivo experiments show that the gene complex has a better penetration effect at pH = 6.6, and the cartilage penetration effect decreases at pH = 7.6, which can effectively anchor in the cartilage matrix site for continuous drug delivery. Further, the composite hydrogel microspheres significantly improve the degeneration of osteoarthritis (OA) cartilage and promote cartilage regeneration. Therefore, the self‐polymerized hydrogel microsphere delivery system with inflammatory response is a promising penetrant/anchoring carrier system for OA treatment.

Advances in surgical treatment for atlantoaxial instability focusing on rheumatoid arthritis: Analysis of a series of 67 patients.

An estimated 88% of rheumatoid arthritis (RA) patients experience various degrees of cervical spine involvement. The excessive movement of the atlantoaxial joint, which connects the occiput to the upper cervical spine, results in atlantoaxial instability (AAI). AAI stabilization is usually achieved by C1 lateral mass-to-C2 pedicle screw-rod fixation (LC1-PC2 fixation), which is technically challenging in RA patients who often show destructive changes in anatomical structures. This study aimed to analyze the clinical results and operative experiences of C1-C2 surgery, with emphasis on the advancement of image-guided surgery and augmented reality (AR) assisted navigation. We presented our two decades of experience in the surgical management of AAI from April 2004 to November 2022. We have performed surgery on 67 patients with AAI, including 21 traumatic odontoid fractures, 20 degenerative osteoarthritis, 11 inflammatory diseases of RA, 5 congenital anomalies of the os odontoideum, 2 unknown etiologies, 2 movement disorders, 2 previous implant failures, 2 osteomyelitis, 1 ankylosing spondylitis, and 1 tumor. Beginning in 2007, we performed LC1-PC2 fixation under C-arm fluoroscopy. As part of the progress in spinal surgery, since 2011 we used surgical navigation from presurgical planning to intraoperative navigation, using the preoperative computed tomography (CT) -based image-guided BrainLab navigation system. In 2021, we began using intraoperative CT scan and microscope-based AR navigation. The technical complexities of C1-C2 surgery can be mitigated by CT-based image-guided surgery and microscope-based AR navigation, to improve accuracy in screw placement and overall clinical outcomes, particularly in RA patients with AAI.

Surgical treatment of knee osteoarthritis focusing on the patellofemoral joint

Background: Surgical management of the osteoarthritic knee joint consists of osteotomies such as a high tibial osteotomy (HTO), uni-compartmental knee arthroplasty (UKA), and total knee arthroplasty (TKA). These surgeries mainly treat the tibiofemoral joint but can also have an impact on the patellofemoral (PF) joint. These changes in PF joint can affect the surgical outcome.Current Concepts: PF joint problems are relative contraindications in UKA. However, recent studies have reported that these problems do not markedly affect the result of UKA. During HTO, the patella height and tracking can change, affecting the PF joint problem. The effect of the PF joint can be minimized through various methods of closing wedge HTO or modified opening wedge (OW) HTO, such as retro-tubercular biplanar OWHTO. However, this method is controversial regarding its impact on clinical outcomes. In TKA, pain caused by PF joint problems can be reduced using techniques such as patella resurfacing, patelloplasty, and denervation; however, there is no clear consensus.Discussion and Conclusion: The surgical treatment of degenerative knee osteoarthritis has an impact on the PF joint, which can affect the outcome of surgery and vice versa. However, these impacts only occasionally cause clinical difference. Conclusively, these surgeries should be done by considering the PF joint because changes in the joint can affect the surgical outcome.

Trends in prevalence and implant types in the Nova Scotia Joint Database Registry between 2005 and 2021.

The aim of this study is to evaluate the change in incidence rate of shoulder arthroplasty, indications, and surgeon volume trends associated with these procedures between January 2003 and April 2021 in the province of Nova Scotia, Canada. A total of 1,545 patients between 2005 and 2021 were analyzed. Patients operated on between 2003 and 2004 were excluded due to a lack of electronic records. Overall, 84.1% of the surgeries (n = 1,299) were performed by two fellowship-trained upper limb surgeons, with the remainder performed by one of the 14 orthopaedic surgeons working in the province. Total shoulder arthroplasty (TSA) was the most frequent procedure (32.17%; n = 497), followed by stemmed hemiarthroplasty (SHA) (27.7%; n = 428). The most frequent indication for primary shoulder arthroplasty was degenerative osteoarthritis (58.1%; n = 882), followed by acute proximal humerus fracture in 15.11% (n = 245), and rotator cuff arthropathy in 14.18% (n = 220). The overall rate of revision was 7.7% (2.8% to 11.2%). The number of TSAs and reverse shoulder arthroplasties (RSAs) has been increasing since 2016. The amount of revision cases is proportional to the number of operations performed in the same year throughout the study period. The incidence of shoulder arthroplasty in the Maritime Provinces has increased over the last 16 years. Revision rates are similar the those found in other large database registries. Reverse shoulder arthroplasty prevalence has increased since 2016.