Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Tackling Osteoarthritic Knee Pain with Electroacupuncture

Electroacupuncture（EA） has been widely used in pain relief. Clinical evidence has revealed its unique advantages and effectiveness in alleviating pain. Studies on EA and pain relief have revealed that EA displays greater analgesic effects for different types of pain in comparison to manual acupuncture. Here, we reviewed the clinical application and mechanism of EA in treating osteoarthritic knee pain and its influence factors in curative effect.

Arthroscopic debridement of osteoarthritic elbow in professional athletes

Background Arthroscopic debridement is an appropriate procedure for osteoarthritic elbow in general populations. However, the results of arthroscopic debridement in the professional athletes, a younger and highly active patient cohort is unclear. The purposes of this study were to assess the clinical outcomes of arthroscopic debridement of osteoarthritic elbow in professional athletes and to evaluate the effect of prognostic factors on the clinical outcomes. Methods From January 1999 to January 2006, 35 professional athletes with osteoarthritc elbow （36 elbows） were treated with arthroscopic debridement, consisted of osteophytes removal, loose bodies removal and fenestration of the olecranon fossa as necessary. Average patient age was （23＋5） years （range 7-34 years）. Average follow-up was （43＋23） months （range 16-98 months）. Athletic activities consisted mainly of wrestling, judo and weightlifting. Patients were evaluated preoperatively and postoperatively with the modified Hospital for Special Surgery （HSS） elbow scoring system. Results According to the modified HSS elbow scoring system, the result was excellent for 16 elbows, good for 14 and poor for 6. No case had got worse after surgery. All athletes reported an improvement in pain. After athletic training, 15 elbows were not painful, 16 mildly painful, 3 moderately painful and 2 severely painful. The arc of flexion-extension improved from 111° preoperatively to 127° postoperatively. All of the athletes were able to return to their previous level of training. Five athletes won national-level championships. At follow-up, 17 athletes （18 elbows） were greatly satisfied with the results, 12 satisfied and 6 unsatisfied. Postoperatively, one athlete reported ulnar nerve symptoms and two others had residual loose bodies. The fenestration of the olecranon fossa was associated with a significantly increased chance of a poor outcome. The nature of the osteoarthdtis, duration of symptoms, osteophytes removal and loose bodies removal did not predict the outcomes. Conclusions Arthroscopic debridement of osteoarthritic elbow in professional athletes can yield significant short-term pain relief, as well as restoration of elbow range of motion and resuming their athletic training. The long-term durability of this procedure with regard to preservation of range of motion and radiographic progression of arthritis remains unknown.

Static and Dynamic Analysis of Osteoarthritic and Orthotic Human Knee

The first objective of this paper is to study the influence of the orthotic device on the maximum values of stresses in knee cartilages by using Ansys Workbench 14.5 software and applying the Finite Element Analysis (FEA) on a virtual assembly composed by an orthotic device and osteoarthritic knee (OAK). The second objective consists into quantifying and investigating the nonlinear motion of the human knee joint for OAK patients, with and without the orthotic device mounted on OAK, using tools of dynamics stability analysis. The short Lyapunov Exponents (LEs) are calculated, as measures of human knee and ankle joints stability, based on the experimental time series collected by using the biometrics acquisition system during walking on horizontal and inclined treadmills from a sample of healthy subjects and a sample of patients suffering by OAK disease. The values of LEs obtained for OAK patients are larger on the inclined treadmill than on horizontal treadmill and are larger than those obtained for healthy knees, being associated with more divergence and less stability. The results confirm that the influence of an orthotic device mounted on OAK on its stability is significant, the values obtained for LEs being smaller than those calculated for OAK, and closer to the values of normal knees of patients and of healthy subjects.

High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration

BACKGROUND High tibial osteotomy(HTO)is a well-established method for the treatment of medial compartment osteoarthritis of the knee with varus deformity.However,HTO alone cannot adequately repair the arthritic joint,necessitating cartilage regeneration therapy.Cartilage regeneration procedures with concomitant HTO are used to improve the clinical outcome in patients with varus deformity.AIM To evaluate cartilage regeneration after implantation of allogenic human umbilical cord blood-derived mesenchymal stem cells(hUCB-MSCs)with concomitant HTO.METHODS Data for patients who underwent implantation of hUCB-MSCs with concomitant HTO were evaluated.The patients included in this study were over 40 years old,had a varus deformity of more than 5°,and a full-thickness International Cartilage Repair Society(ICRS)grade IV articular cartilage lesion of more than 4 cm2 in the medial compartment of the knee.All patients underwent second-look arthroscopy during hardware removal.Cartilage regeneration was evaluated macroscopically using the ICRS grading system in second-look arthroscopy.We also assessed the effects of patient characteristics,such as trochlear lesions,age,and lesion size,using patient medical records.RESULTS A total of 125 patients were included in the study,with an average age of 58.3±6.8 years(range:43-74 years old);95(76%)were female and 30(24%)were male.The average hip-knee-ankle(HKA)angle for measuring varus deformity was 7.6°±2.4°(range:5.0-14.2°).In second-look arthroscopy,the status of medial femoral condyle(MFC)cartilage was as follows:73(58.4%)patients with ICRS grade I,37(29.6%)with ICRS grade II,and 15(12%)with ICRS grade III.No patients were staged with ICRS grade IV.Additionally,the scores[except International Knee Documentation Committee(IKDC)at 1 year]of the ICRS grade I group improved more significantly than those of the ICRS grade II and III groups.CONCLUSION Implantation of hUCB-MSCs with concomitant HTO is an effective treatment for patients with medial compartment osteoarthritis and varus deformity.Regeneration of cartilage improves the clinical outcomes for the patients.

Regenerative Engineering for Knee Osteoarthritis Treatment： Biomaterials and Cell-Based Technologies

Knee osteoarthritis （OA） is the most common form of arthritis worldwide. The incidence of this disease is rising and its treatment poses an economic burden. Two early targets of knee OA treatment include the predominant symptom of pain, and cartilage damage in the knee joint. Current treatments have been beneficial in treating the disease but none is as effective as total knee arthroplasty （TKA）. However, while TKA is an end-stage solution of the disease, it is an invasive and expensive procedure, Therefore, innovative regenerative engineering strategies should be established as these could defer or annul the need for a TKA. Several biomaterial and cell-based therapies are currently in development and have shown early promise in both preclinical and clinical studies. The use of advanced biomaterials and stem cells independently or in conjunction to treat knee OA could potentially reduce pain and regenerate fo- cal articular cartilage damage. In this review, we discuss the pathogenesis of pain and cartilage damage in knee OA and explore novel treatment options currently being studied, along with some of their limitations.

Microarray analysis of signalling interactions between inflammation and angiogenesis in subchondral bone in temporomandibular joint osteoarthritis

Inflammation and angiogenesis,the major pathological changes of osteoarthritis(OA),are closely associated with joint pain;however,pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated.Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint.Microarray-based transcriptome analysis,besides quantitative real-time polymerase chain reaction,was performed to identify differentially expressed genes(DEGs).Overall,182 DEGs(fold change≥2,P<0.05)were identified between the control and unilateral anterior crossbite groups:168 were upregulated and 14 were downregulated.On subjecting significant DEGs to enrichment analyses,inflammation and angiogenesis were identified as the most affected.Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling.Furthermore,angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling.Protein-protein interaction analysis revealed a close interaction between inflammation-and angiogenesis-related DEGs,suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(Pi3kcd),cathelicidin antimicrobial peptide(Camp),C-X-C motif chemokine receptor 4(Cxcr4),and MYB proto-oncogene transcription factor(Myb)play a central role in their interaction.To summarize,our findings reveal that in subchondral bone of osteoarthritic joints,signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain;moreover,our data highlight potential targets for the inhibition of OA pain.

Loose Body in the Knee Joint: A Case Report

Background: Loose bodies (LBs) within the knee joint are commonly encountered during clinical practice and are frequently observed during knee arthroscopy. The primary treatment involves the removal of loose bodies;however, their complete eradication is often challenging and may not address underlying diseases, leading to persistent symptoms and the risk of new loose body formation. Aim: This case report aims to present the findings and surgical management of a 52-year-old male with an unusually large osseous loose body in the knee joint and associated pathologies. Case Presentation: The patient, a 52-year-old male, experienced recurrent episodes of severe, sudden, and painful locking of the knee joint, leading to difficulties moving. A plain MRI study was conducted to evaluate the condition of the knee joint, which revealed various degenerative changes and the presence of a loose body. Subsequently, an arthroscopic examination was performed under general anesthesia, uncovering the presence of an abnormally large loose body, as well as other pathologies including chondropathy, meniscal degeneration, and Baker’s cyst. Conclusion: Loose bodies (LBs) in the knee joint pose significant challenges and may lead to debilitating symptoms. Timely diagnosis and appropriate surgical intervention are crucial for symptom relief and the prevention of further joint damage as arthroscopic excision. Comprehensive imaging has a vital role in guiding treatment decisions and optimizing patient outcomes. In this case, the removal of the loose body improved patient outcomes and helped prevent potential joint complications.