Cartilage Research Articles

Short-term manual acupuncture decreased markers of systemic inflammation and altered articular cartilage transcripts in the Dunkin-Hartley model of osteoarthritis.

To investigate indicators of mobility, inflammation, and cartilage remodeling in Dunkin-Hartley guinea pigs (Cavia porcellus) treated with manual acupuncture compared to 2 different comparator acupuncture groups. 12-month-old male Hartleys were randomly assigned to 1 of 3 in vivo experimental groups that received manual acupuncture, needle sheath taps on corresponding acupoints, or off-point acupuncture. Treatments were performed under isoflurane once weekly for 3 weeks, and open-field enclosure monitoring was performed at the same frequency. After final treatments, all animals were euthanized, blood was collected for inflammatory marker analysis, and tissues were collected for histology, immunohistochemistry, and transcript expression analysis. 18 animals were involved: 6 per experimental group. Serum concentrations of complement component 3 and prostaglandin E2 were significantly decreased in the acupuncture group (P < .05). Muscle from acupoint stomach-36 had 6 gene transcripts with altered expressions in the manual acupuncture group compared to comparators. From cartilage/menisci, manual acupuncture resulted in the downregulation of 13 gene transcripts. Nerve growth factor (NGF) immunostaining in all 3 layers of articular cartilage of the medial tibial plateau was greater in the manual acupuncture group relative to the comparator groups. There were no differences in enclosure monitoring parameters or histologic grading. Appreciable changes in voluntary mobility, behavioral or serum biochemical parameters, or stifle histological structure were not seen. Differences in serum inflammatory proteins, the gene expression of cartilage-remodeling transcripts, and NGF protein concentrations in cartilage were elucidated. The short duration of manual acupuncture showed the initiation of beneficial regenerative and remodeling processes.

Arthroscopic synovitis severity scoring in canine stifles with cranial cruciate ligament disease.

To investigate the occurrence, degree, and risk factors associated with arthroscopic stifle joint synovitis in dogs with cranial cruciate ligament (CCL) disease. Retrospective, observational study. Canine CCL disease (n = 163) from 149 dogs and their arthroscopic video recordings. Arthroscopic video recordings were reviewed. A synovitis severity (0-5) and a modified Outerbridge cartilage classification system score were assigned, along with recording the presence or absence of a medial meniscal bucket handle tear. Medical records were reviewed for age, sex, limb, and duration of clinical signs. Univariate analyses were performed via a Fisher's exact test for categorical independent variables, and ordered logistic regression was used for continuous variables. Multivariable ordered logistic regression considered independent variables with a p-value <.2 on univariate analyses. p-value <.05 was considered statistically significant. Synovitis was identified in 100% of the stifles examined. The most frequent synovitis severity score was 3/5. Univariate analysis showed a significant association between synovitis severity score and bodyweight (p = .005), median cartilage score (p = .002), and being female (p = .032). On multivariable analysis, the synovitis severity score was significantly associated with median cartilage score (p = .042) and duration of clinical signs (p < .001). Synovitis was arthroscopically always identified in stifles with CCL disease. The severity of synovitis was associated with more progressive damage to the articular cartilage and a longer duration of clinical signs. Earlier intervention in dogs with CCL disease may be warranted to decrease synovitis and progression of osteoarthritis.

Accuracy and safety of two landmark-guided techniques for arthrocentesis and intra-articular injection of the shoulder in dogs.

To determine the accuracy and safety of two landmark-guided techniques for shoulder arthrocentesis and injection. Ex vivo prospective study. A total of 36 paired canine cadaver forelimbs. An electronic survey was used to assess the prevalence of injection technique amongst surgeons in clinical practice. Thoracic limbs were randomized to technique for shoulder arthrocentesis and injection (subacromial [SA], n = 18, or supratubercular [ST], n = 18). Repositions, attempts, and the acquisition of synovial fluid was recorded. After the needle was placed, contrast was injected into the joint to determine accuracy of position. The radiographic presence of intra-articular contrast was judged as an accurate injection. Shoulders were disarticulated and India ink assay performed to assess for iatrogenic articular cartilage injury (IACI). Both SA and ST techniques were not accurate. Completely accurate injection was identified in 50% SA and 44% ST (p = .80). IACI was identified in 50% SA versus 11% ST (p = .027). There were no significant differences in repositions, attempts, presence of synovial fluid (p = .5, p = .6, p = .7). Landmark-guided shoulder injections performed via SA and ST approaches in cadaveric dog shoulders are overall inaccurate. If performing landmark-guided shoulder injection, ST technique carries a lower risk of IACI than SA in cadaveric shoulders. Landmark-guided shoulder injections are inaccurate in dogs and may result in treatment failure. A ST approach may be considered preferable due to the lower risk of cartilage damage. Future studies should assess ultrasound-guided techniques to improve accuracy and safety.

A Cadaveric Study of the Sagittal Patellar Insertion of the Medial Patellofemoral Ligament in Children: Implications for Reconstruction.

Patellofemoral instability is a common problem, and medial patellofemoral ligament (MPFL) reconstruction is a standard treatment approach for recurrent instability. The accurate restoration of anatomy in MPFL reconstruction is essential. While coronal-plane anatomy of the MPFL patellar insertion has been previously reported, sagittal-plane anatomy has not been widely studied. To evaluate the sagittal patellar insertion of the MPFL in pediatric specimens to guide future anatomic reconstruction. Descriptive laboratory study. A total of 11 pediatric cadaveric knee specimens were dissected. The patella and sagittal MPFL insertion were evaluated. The maximal anterior-posterior patellar width, distance from the posterior patella to the posterior MPFL insertion, distance from the medial patellar articular cartilage edge to the MPFL insertion, maximal MPFL thickness, and distance from the anterior MPFL insertion to the anterior patella were measured. The proportion of patellar coverage by the sagittal MPFL insertion footprint was calculated. The pediatric knee specimens had a mean age of 9.3 ± 1.4 years (range, 6-11 years). The mean maximal transverse patellar width was 19.0 ± 2.7 mm (range, 13.7-22.7 mm). The mean posterior patella-to-posterior MPFL distance was 10.5 ± 1.6 mm (range, 7.7-12.6 mm). The mean patellar articular cartilage edge-to-MPFL distance was 2.3 ± 0.6 mm (range, 1.5-3.5 mm). The mean maximal MPFL thickness was 4.0 ± 0.9 mm (range, 2.6-5.5 mm). The mean anterior MPFL-to-anterior patella distance was 4.4 ± 1.1 mm (range, 2.6-5.8 mm). The sagittal MPFL insertion footprint spanned a mean of 21.0% (range, 16.1%-29.7%) of the medial patella. This study, utilizing skeletally immature cadaveric specimens, demonstrated that the sagittal MPFL insertion consistently resided in the anterior third of the patella, averaging 21% of the total sagittal patellar width. Additionally, the distance from the MPFL insertion to the medial patellar articular cartilage edge showed minimal variation, representing a consistent intraoperative landmark for MPFL graft placement. This research characterized MPFL insertion anatomy on the medial patella in the sagittal plane. This knowledge provides a clear target area for anatomic graft placement during MPFL reconstruction.

Significance of tibial-tubercle trochlear groove distance and adjunctive radiological parameters in patients with recurrent patellar instability.

Magnetic resonance imaging (MRI) is often used to evaluate patients with patellar dislocations to facilitate diagnosis and management strategies. Many radiological parameters have been described in the literature. The aim of this study was to assess the significance of tibial-tubercle trochlear groove distance (TT-TG) distance and other MRI measurements in patients with and without patellar instability. This case-control study included 41 patients with recurrent patellar instability and 50 patients with stable knees, all of whom underwent MRI scans. A total of 19 radiological parameters were measured in both groups. All measured MRI parameters had statistically significant differences between both groups (p < 0.05) apart from trochlear cartilage length. TT-TG distance. 20mm had the strongest association with patellar instability (OR 53.3, p = 0.006, 95%CI [3.1- 927.4]) and the highest specificity (100%) but had the lowest sensitivity (34%) out of all the measured parameters. TT-TG. 13mm had a higher sensitivity (68%) but lower specificity (72%) and weaker association with patellar instability (OR 5.5, p < 0.001, 95%CI [2.2. 13.7]). TT-TG/trochlear articular cartilage width ratio also had a strong association with patellar instability (OR 14.7, p < 0.001, 95%CI [4.5. 48.5]) with high specificity (92%) but lower sensitivity (56%). The cut-off values for TT-TG distance at 13mm and 20mm both had advantages and disadvantages which supports the concept of using patient-individualised ratios. Patellar instability is associated with many radiological abnormalities demonstrated on MRI scans. Selection of the most appropriate measurement is dependent on the philosophy and preference of the treating clinician.

Three-dimensional cell culture-derived extracellular vesicles loaded alginate/hyaluronic acid composite scaffold as an optimal therapy for cartilage defect regeneration.

Osteoarthritis (OA) is a chronic musculoskeletal disease characterized by joint inflammation and progressive degeneration of articular cartilage. Currently a definitive cure for OA remains to be a challenge due to the very low self-repair capacity of cartilage, thus development of more effective therapies is needed for cartilage repair. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown great potential as therapeutic agents for stimulating regeneration of articular cartilage. However, a standardized protocol is still lacking for manufacturing of highly active EVs for clinical applications. This study aimed to investigate the efficient production of highly active EVs by 3-dimensional (3D) MSC culture, verify the reparative efficacy of EVs on cartilage defect and elucidate the repair mechanisms. Umbilical cord MSCs were embedded in alginate to form MSC spheroids for 3D culture in human platelet lysate (hPL)-containing medium, which produced 3D culture-derived EVs (3D-EVs) with a significantly improved yield. The 3D-EVs expressed higher level of VEGF, and appeared superior to 2D monolayer MSC culture-derived EVs (2D-EVs) to improve migration and proliferation in MSCs and inflammatory chondrocytes, and to suppress expression of cartilage-degrading factors. Importantly, the 3D-EVs and sodium alginate (SA)-hyaluronic acid (HA) composite hydrogel (3D-EVs/SA-HA) demonstrated significantly improved therapeutic efficacy than 2D-EVs/ SA-HA hydrogel for repair of cartilage defect in vivo. The underlying mechanisms are associated with the concomitant upregulation of type II collagen and cartilage synthesis and downregulation of MMP13 in cartilage tissues. Collectively, these data showed that highly active MSC EVs could be efficiently manufactured by 3D cell culture with hPL-containing medium, and these EVs were superior to 2D-EVs for the repair of articular cartilage defect.

Investigation of customized total knee implant with articular cartilage under loading conditions using finite element analysis.

Knee osteoarthritis (KOA) is a degenerative joint disease predominantly affecting the elderly and is often managed through knee replacement surgeries. West Asians, who frequently engage in activities involving bending and kneeling during their prayers, tend to exhibit distinct bone anatomy compared to the Caucasian population. This research posits that patient-specific, customized knee implants with articular cartilages may lead to reduced post-surgical discomfort and a better implant fit compared to conventional standard implants. This study presents a novel concept and approach for the development of a customized total knee implant with articular cartilages, specifically tailored to simulate loading conditions using finite element analysis (FEA) for the Saudi Arabian population. The research analyses patient-specific customized knee implants with articular cartilages under both pre- and post-implant conditions using a finite element model (FEM). Computed tomography (CT) images of patients were utilized to create a solid model, which was then analysed under various constraints and conditions. The meshing process employed tetrahedral elements, converging with 76,197 nodes and 43,009 elements. The analysis was conducted under different body weights, specifically 75-80 kg and 100-105 kg. Two sets of force and moment were applied: the first with a force of 1000 N and a moment of 1.5 N-m, and the second with a force of 750 N and a moment of 0.8 N-m. The results indicated a 5% reduction in stress with implants designed for a 100 kg body weight, along with a significant reduction in ligament strain when compared to conventional knee joint stresses. This study offers a promising pathway toward reducing post-surgical discomfort. The proposed innovative solution has the potential to revolutionize total knee implant technology, offering enhanced functionality and improved patient outcomes for the Saudi Arabian population.

In situ swelling of low-friction, high load-bearing self-bending bilayer hydrogels inspired by articular cartilage

The articular cartilage is characterized by its gradient hierarchical structure, which exhibits excellent lubrication and robust load-bearing properties. However, its inherent difficulty in self-repair after damage presents numerous formidable challenges for cartilage repair. Inspired by the unique structure of articular cartilage, a biomimetic bilayer hydrogel composed of PAM (polyacrylamide) and PAM/SA (sodium alginate) is prepared using a two-stepin-situswelling method. The bilayer hydrogel demonstrates exceptional structural stability due to the interlayerin-situchemical cross-linking. Compared to monolayer hydrogels, the PAM-PAM/SA bilayer hydrogel demonstrates superior mechanical attributes, exhibiting a compressive strength of 1 MPa and a compressive modulus of 0.22 MPa. Furthermore, exploration of the tribological performance of the PAM-PAM/SA bilayer hydrogel have revealed its low-friction performance under high loads, with a coefficient of friction as low as 0.032. Finally, leveraging the differential swelling properties between the distinct layers of the PAM-PAM/SA bilayer hydrogel, a self-bending biomimetic cartilage capable of conforming to complex joint surfaces is fabricated. This highly lubricating, mechanically robust, and conformal biomimetic cartilage provides an effective means for addressing cartilage defects and joint diseases.

Stromal Vascular Fraction of Adipose Tissue: Prospects for Use in the Treatment of Osteoarthritis and Articular Cartilage Injuries (Literature Review)

Summary. Osteoarthritis (OA) is a chronic, progressive, degenerative-dystrophic joint disease primarily caused by damage to the articular cartilage. Conservative pharmacological treatment of OA consists of prescribing nonsteroidal anti-inflammatory drugs, chondroprotectors, hyaluronic acid injections, and therapeutic blockades with glucocorticosteroids. The use of orthobiological agents represents an alternative method in OA treatment. Among the variety of orthobiological approaches, adipose tissue serves as a new and attractive source of stem cells for the treatment of OA. The stromal vascular fraction creates an environment where stem cells can interact and stimulate regeneration.

Histopathologic spectrum and clinical management of pharyngeal and laryngeal sarcomas.

Sarcomas are rare mesenchymal malignancies (<1% of all cancer types), with 5-15% occurring in the head and neck. Common types include osteosarcoma, chondrosarcoma, and rhabdomyosarcoma. They often recur and have poor survival rates. Treatment involves surgery, radiation, and/or chemotherapy, utilizing a multidisciplinary approach. This study aims to overview sarcomas at our hospital and illustrate the interdisciplinary management of pharyngeal and laryngeal cases. This single-center study provides a comprehensive analysis of head and neck sarcomas (HNS) and examines interdisciplinary treatment approaches for pharyngeal and laryngeal sarcomas in patients treated at the Department of Head and Neck Surgery, Technical University of Munich, from 2007 to 2022. The study encompasses data on age, gender, histopathological diagnoses, treatment modalities, follow-up, and outcomes, with an emphasis on histopathological findings and collaborative therapeutic strategies. 27 cases of HNS were identified (2007-2022). Among these, 11 were pharyngeal or laryngeal sarcomas. All pharyngeal sarcomas underwent primary resection with reconstruction based on tumor location and extent. In laryngeal sarcomas, three required laryngectomy, one had a hemilaryngectomy, and one patient opted for primary radiochemotherapy over laryngopharyngectomy. Adjuvant radiotherapy was given in 5 cases, and radiochemotherapy in 3. Diagnoses included a range of soft tissue and bone sarcomas, such as liposarcoma, synovial sarcoma, and osteosarcoma. During the study period, 4 patients survived, 5 patients were noted as deceased, and survival data for 2 patients remain unavailable. Patients exhibited an average survival of 7,6 (± 10,4) years. The survival times within this limited patient population exhibit significant variation. Histologically, a wide spectrum of low and high-grade soft tissue and bone sarcomas were diagnosed including liposarcoma, synovial sarcoma, Ewing, osteo- or chondrosarcoma. HNS are rare and challenging to treat. Surgery is the primary treatment, with postoperative radiotherapy recommended for incomplete resections or high-risk subtypes. Advanced surgical techniques and reconstruction allow for radical resections while preserving function. Incorporating genetic insights and better sarcoma classification can further optimize treatments.

HDAC4 regulates apoptosis in Acan-CreERT2;HDAC4d /d mice with osteoarthritis by downregulating ATF4.

Several studies have previously shown that histone deacetylase 4 (HDAC4) can regulate endoplasmic reticulum stress-induced apoptosis through the activating transcription factor 4 (ATF4)/CAAT/enhancer binding protein homologous (CHOP) signaling pathway, thereby affecting the progression of osteoarthritis (OA). The present study investigated the regulatory mechanism of HDAC4 in chondrocyte apoptosis in OA using Acan-CreERT2;HDAC4fl/fl gene knockout mice. Forty mice were divided into four groups: TM-DMM group [tamoxifen (TM) injection at 2 months of age and destabilization of the medial meniscus (DMM) surgery at 3 months], TM-sham group (TM injection at 2 months of age and sham surgery at 3 months), no TM-DMM group (corn oil injection at 2 months of age and DMM surgery at 3 months) and no TM-sham group (corn oil injection at 2 months of age and sham surgery at 3 months). Apoptosis and cartilage damage were assessed through imaging, histological analysis, immunohistochemistry, reverse transcriptase-PCR and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. HDAC4 knockdown resulted in increased osteophyte formation, significant narrowing of the joint space and increased articular cartilage damage. Furthermore, expression levels of key apoptosis-related markers, ATF4, CHOP, caspase-3 and caspase-9, were significantly higher in the TM groups than in their respective control groups. Taken together, our results suggest that HDAC4 deficiency leads to increased apoptosis induced by the ATF4/CHOP signaling pathway in the pathogenesis of OA. Therefore, upregulation of HDAC4 may represent a potential therapeutic strategy.

Increased oxidative phosphorylation through pyruvate dehydrogenase kinase 2 deficiency ameliorates cartilage degradation in mice with surgically induced osteoarthritis.

Chondrocytes can shift their metabolism to oxidative phosphorylation (OxPhos) in the early stages of osteoarthritis (OA), but as the disease progresses, this metabolic adaptation becomes limited and eventually fails, leading to mitochondrial dysfunction and oxidative stress. Here we investigated whether enhancing OxPhos through the inhibition of pyruvate dehydrogenase kinase (PDK) 2 affects the metabolic flexibility of chondrocytes and cartilage degeneration in a surgical model of OA. Among the PDK isoforms, PDK2 expression was increased by IL-1β in vitro and in the articular cartilage of the DMM model in vivo, accompanied by an increase in phosphorylated PDH. Mice lacking PDK2 showed significant resistance to cartilage damage and reduced pain behaviors in the DMM model. PDK2 deficiency partially restored OxPhos in IL-1β-treated chondrocytes, leading to increases in APT and the NAD+/NADH ratio. These metabolic changes were accompanied by a decrease in reactive oxygen species and senescence in chondrocytes, as well as an increase in the expression of antioxidant proteins such as NRF2 and HO-1 after IL-1β treatment. At the signaling level, PDK2 deficiency reduced p38 signaling and maintained AMPK activation without affecting the JNK, mTOR, AKT and NF-κB pathways. p38 MAPK signaling was critically involved in reactive oxygen species production under glycolysis-dominant conditions in chondrocytes. Our study provides a proof of concept for PDK2-mediated metabolic reprogramming toward OxPhos as a new therapeutic strategy for OA.

Experimental investigation on the reverse mechano-electrical effect of porcine articular cartilage

IntroductionThe electric signals within the cartilage tissue are essential to biological systems and play a significant role in cartilage regeneration. Therefore, this study analyzed and investigated the reverse mechano-electrical effect in porcine articular cartilage and its related influencing factors.MethodsThe deflection of cartilage samples in an electric field was measured to analyze the mechanisms of different factors affecting the reverse mechano-electrical effect in articular cartilage.ResultsThe results showed that the cartilage thickness, water content, and externally applied voltage all impacted the deflection of the cartilage. The reduction in cartilage water content resulted in a decrease in cartilage thickness, following the same influencing mechanism as thickness. On the other hand, an increase in the externally applied voltage led to an increase in the electric field force within the cartilage space, consequently increasing the deflection of the cartilage in the electric field. Additionally, the externally applied voltage also caused a slight temperature rise in the vicinity of the cartilage specimens, and the magnitude of the temperature increase was proportional to the externally applied voltage.DiscussionThe fitting results of the experimental data indicated that cartilage thickness influenced the dielectric constant and moment of inertia of the cartilage in the electric field, thereby affecting the magnitude of the electric field force and deflection of the cartilage. This may provide valuable insights for further investigation into the microscopic mechanisms of cell proliferation, differentiation, and cartilage regeneration induced by electrical stimulation.

A miR-activated hydrogel for the delivery of a pro-chondrogenic microRNA-221 inhibitor as a minimally invasive therapeutic approach for articular cartilage repair.

Articular cartilage has limited capacity for repair (or for regeneration) under pathological conditions, given its non-vascularized connective tissue structure and low cellular density. Our group has successfully developed an injectable hydrogel for cartilage repair, composed of collagen type I (Col I), collagen type II (Col II), and methacrylated-hyaluronic acid (MeHA), capable of supporting chondrogenic differentiation of mesenchymal stem cells (MSCs) towards articular cartilage-like phenotypes. Recent studies have demonstrated that silencing miR-221 may be an effective approach in promoting improved MSC chondrogenesis. Thus, this study aimed to develop a miR-activated hydrogel capable of offering a more effective and less invasive therapeutic approach to articular cartilage repair by delivering a pro-chondrogenic miR-221 inhibitor to MSCs using our MeHA-Col I/Col II hydrogel. The MeHA-Col I/Col II hydrogel was cast as previously shown and incorporated with cells transfected with miR-221 inhibitor (using a non-viral peptide delivery vector) to produce the miR-activated hydrogel. Down-regulation of miR-221 did not affect cell viability and enhanced MSCs-mediated chondrogenesis, as evidenced by significantly upregulated expression of key pro-chondrogenic articular cartilage genes (COL2A1 and ACAN) without promoting hypertrophic events (RUNX2 and COL10A1). Furthermore, miR-221 down-regulation improved cartilage-like matrix formation in the MeHA-Col I/Col II hydrogel, with significantly higher levels of sulfated glycosaminoglycans (sGAG) and Col II produced by MSCs in the hydrogel. These results provide evidence of the potential of the miR-activated hydrogel as a minimally invasive therapeutic strategy for articular cartilage repair.

Kojic acid alleviates osteoarthritis by attenuating inflammation and restoring impaired autophagy through regulating NF-κB and PI3K/AKT/mTOR signaling pathways: An in vivo and in vitro study.

Osteoarthritis (OA) is the most prevalent joint disorder globally, causing a substantial and increasing socioeconomic burden. Kojic acid (KA) presented potential biological roles in regulating inflammation and autophagy, which was implicated in OA progression. However, its role in chondrocytes and OA has not been reported. To do so, this study aims to explore the chondroprotective effect of KA and elucidate its regulatory mechanisms. IL-1β in vitro was used to induce OA-like phenotypes. Cell viability was measured by cell counting kit-8 assay. RT-qPCR, western blotting, as well as immunofluorescence staining were used to assess protein and RNA expression of inflammatory (COX2 and iNOS), catabolic (MMP13 and MMP3), anabolic (collagen II, aggrecan and SOX9), and signaling pathways factors. Destabilized medial meniscus (DMM) surgery was adopted to build OA model in vivo. After consecutive 8weeks of intra-articular injection of KA, X-ray, μ-CT, histological staining, as well as immunohistochemistry staining were adopted to evaluate effects of KA on articular cartilage in vivo. KA did not affect chondrocyte viability. KA notably elevated anabolic factors expression, simultaneously, inhibited catabolic and inflammatory factors expression in vitro. Mechanistically, KA significantly suppressed the activated NF-κB and PI3K/AKT/mTOR signaling pathways. Moreover, impaired autophagy was restored by KA. Inhibition of autophagy by 3-MA diminished the chondroprotective effect of KA. Intra-articular injection of KA can significantly alleviate DMM-induced cartilage damage in vivo. Collectively, our work is the first to demonstrate that KA can alleviate osteoarthritis by attenuatinginflammationand restoring impaired autophagy through regulating relevant signaling pathways. This in vivo and in vitro study provides strong evidence supportingKA as a novel and valuable approach for treating OA.

A computational study on dynamic behavior of articular cartilage under cyclic compressive loading and magnetic field.

The dynamic behavior of articular cartilage (a soft porous biological tissue) with strain-dependent nonlinear permeability under cyclic compressive loading and magnetic field is investigated computationally. The compressive force is applied on top surface of the cylindrical plug of the tissue by means of a porous filter. The study of mechanical and deformational behavior of soft porous tissues such as articular cartilage under dynamic compressive loading and magnetic field is useful in understanding the underlying mechano-biological process that may lead to the development of a treatment and recovery protocol in a diseased state. In the present study, a linear biphasic mixture theory of porous media has been employed to derive the governing equations in terms of solid displacement and interstitial fluid pressure in the tissue. Exact solutions for the solid displacement, fluid pressure, and relative fluid velocity are provided for the constant permeability case which have also been used to validate the numerical method. On the other hand, the full nonlinear problem has been solved numerically using the method of lines and the outcomes are presented graphically to assess the effects of various emerging parameters. The results indicate that there is an increase in the solid dilatation due to application of magnetic field and this effect is more prominent at relatively high loading frequencies. In general, a repeated compressive force has generated an oscillating positive-negative hydrostatic pressure within the tissue, however, a strong magnetic field at comparatively high loading frequency enforces the tissue to have only the positive (supra-ambient) pressure. The outcomes have also revealed that the pattern of the dynamic behavior of the tissue is strongly dependent on the loading frequency. A considerable phase shift in the dilatation and fluid pressure has been noticed due to the loading frequency as well as magnetic effects. It has also been found that the permeability parameter has a minimal impact on the solid deformation and fluid pressure in all scenarios with a very small phase shift.

Lipidomics unravels lipid changes in osteoarthritis articular cartilage.

Osteoarthritis (OA) is linked to disrupted lipid metabolism. We aimed to profile the lipid composition of human articular cartilage, investigate OA-associated lipidome changes, and explore biological effects. Lipidomic profiling and computational analyses were performed on human articular chondrocytes (hACs) from non-OA (n = 13) and OA (n = 14) hips. Lipid changes were confirmed in the destabilisation of the medial meniscus (DMM) mouse model. The effect of specific lipids was evaluated by in vitro supplementation and gene silencing. We identified 573 lipid species covering 11 lipid classes in hACs. OA and non-OA hACs showed distinct lipid profiles. Most ceramides and dihydroceramides were increased, while cholesteryl esters, diacylglycerols, triacylglycerols, sphingomyelins, hexosylceramides, and lactosylceramides were predominantly decreased in OA chondrocytes. Most upregulated lipids in OA contained C18:1, C20:4, or C22:4 side chains. Many downregulated lipids contained C18:2 or odd-chain C17:0. Lipid profiling of articular cartilage from the DMM mouse model paralleled changes in OA hACs, including odd-chain C17:0 reduction. Further analysis showed that deficiency in enzyme 2-hydroxyacyl-CoA lyase 1 (HACL1), responsible for odd-chain fatty acid synthesis, leads to accumulation of 2-hydroxy C18:0, precursor of C17:0, which results in a shift in hACs from an anabolic to a catabolic state. Our study maps the hAC lipid composition and highlights changes in lipid profiles associated with OA. Dysregulation of certain lipids, especially odd-chain fatty acids, linked to a deficiency in the enzyme HACL1, leads to pathological changes. This understanding opens potential avenues for therapies aimed at targeting lipid imbalances to slow down or treat OA.

Muscle-to-bone and soft tissue-to-bone ratios in track and field athletes.

The purpose of this study was to compare the muscle-to-bone (MBR) and soft tissue-to-bone ratios (SBR) of 459 track and field athletes across event groups to identify differences in MBR and SBR. Dual X-ray absorptiometry provided total and regional (i.e., arm, leg, trunk) lean mass (LM), fat mass (FM), and bone mineral content (BMC). MBR was calculated by dividing LM by BMC. The SBR was calculated by dividing LM+FM by BMC. Kruskal-Wallis tests were used to compare ratios across event groups. Dunn's post-hoc tests were utilized to adjust for multiple comparisons. Total MBR for females was higher in the throwers compared to the multievent athletes (p=0.02). For the males, total MBR was lower in jumpers compared to all events except pole vaulters (PV) (p<0.05). Trunk MBR was higher in the long-distance runners (LD) compared to jumpers, PV, and throwers (p<0.05). The throwers had higher total, arm, and leg SBRs compared to the jumpers, LD, middle distance, PV, and sprint groups (p<0.05). Significant differences in total and regional MBR and SBR were identified across event groups for both sexes, and may indicate event-specific adaptations impacting the balance between soft tissue and bone.

Podium Presentation Title: Comparison of Clinical Outcomes and Return to Sport Rates Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint

Podium Presentation Title: Comparison of Clinical Outcomes and Return to Sport Rates Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint

Blocking the CCL5/CCL7-CCR1 axis regulates macrophage polarization through NF-κB pathway to alleviate the progression of osteoarthritis.

To study the effect of CCR1 and its ligands on macrophage polarization and evaluate its effect on chondrocytes in relieving the progression of osteoarthritis. RAW cells were polarized to M1/M2 subtype, and then different concentrations of BX471 were added to selectively inhibit CCR1. The polarization of the cells was detected by RT-qPCR, immunofluorescence and flow cytometry. CCL5 and CCL7 genes were silenced by SiRNA and its role in macrophage polarization was analyzed. Macrophage conditioned medium was further used to stimulate chondrocytes. Histological observation was carried out on models of medial meniscus (DMM) with or without BX471 treatment. We found that blocking of CCR1 and silencing of its ligand, CCL5 and CCL7, reduced the polarization of M1 macrophages. In terms of mechanism, we found that blocking CCR1 could reduce the activation of NF-κB pathway and inhibit the phosphorylation of IKK, IκBα and P65. In addition, blocking of CCR1 could also reduce cartilage injury induced by macrophage conditioned medium. In vivo, blocking of CCR1 reduced the infiltration and accumulation of M1 macrophages and alleviated articular cartilage injury. CCL5/CCL7-CCR1 axis was involved in macrophage polarization, and blocking it could reduce synovitis and alleviate the process of OA.