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BMC Musculoskeletal Disorders Jun 2024The present study evaluated whether the lack of histone deacetylase 4 (HDAC4) increases endoplasmic reticulum stress-induced chondrocyte apoptosis by releasing...
BACKGROUND
The present study evaluated whether the lack of histone deacetylase 4 (HDAC4) increases endoplasmic reticulum stress-induced chondrocyte apoptosis by releasing activating transcription factor 4 (ATF4) in human osteoarthritis (OA) cartilage degeneration.
METHODS
Articular cartilage from the tibial plateau was obtained from patients with OA during total knee replacement. Cartilage extracted from severely damaged regions was classified as degraded cartilage, and cartilage extracted from a relatively smooth region was classified as preserved cartilage. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to detect chondrocyte apoptosis. HDAC4, ATF4, and C/EBP homologous protein (CHOP) expression levels were measured using immunohistochemistry staining and real-time quantitative PCR. Chondrocytes were transfected with HDAC4 or HDAC4 siRNA for 24 h and stimulated with 300 µM HO for 12 h. The chondrocyte apoptosis was measured using flow cytometry. ATF4, CHOP, and caspase 12 expression levels were measured using real-time quantitative PCR and western blotting. Male Sprague-Dawley rats (n = 15) were randomly divided into three groups and transduced with different vectors: ACLT + Ad-GFP, ACLT + Ad-HDAC4-GFP, and sham + Ad-GFP. All rats received intra-articular injections 48 h after the operation and every three weeks thereafter. Cartilage damage was assessed using Safranin O staining and quantified using the Osteoarthritis Research Society International score. ATF4, CHOP, and collagen II expression were detected using immunohistochemistry, and chondrocyte apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining.
RESULTS
The chondrocyte apoptosis was higher in degraded cartilage than in preserved cartilage. HDAC4 expression was lower in degraded cartilage than in preserved cartilage. ATF4 and CHOP expression was increased in degraded cartilage. Upregulation of HDAC4 in chondrocytes decreased the expression of ATF4, while the expression of ATF4 was increased after downregulation of HDAC4. Upregulation of HDAC4 decreased the chondrocyte apoptosis under endoplasmic reticulum stress, and chondrocyte apoptosis was increased after downregulation of HDAC4. In a rat anterior cruciate ligament transection OA model, adenovirus-mediated transduction of HDAC4 was administered by intra-articular injection. We detected a stronger Safranin O staining with lower Osteoarthritis Research Society International scores, lower ATF4 and CHOP production, stronger collagen II expression, and lower chondrocyte apoptosis in rats treated with Ad-HDAC4.
CONCLUSION
The lack of HDAC4 expression partially contributes to increased ATF4, CHOP, and endoplasmic reticulum stress-induced chondrocyte apoptosis in OA pathogenesis. HDAC4 attenuates cartilage damage by repressing ATF4-CHOP signaling-induced chondrocyte apoptosis in a rat model of OA.
Topics: Animals; Apoptosis; Chondrocytes; Rats, Sprague-Dawley; Activating Transcription Factor 4; Histone Deacetylases; Male; Rats; Endoplasmic Reticulum Stress; Cartilage, Articular; Humans; Disease Models, Animal; Osteoarthritis, Knee; Female; Middle Aged; Aged; Transcription Factor CHOP; Cells, Cultured; Osteoarthritis; Repressor Proteins
PubMed: 38879481
DOI: 10.1186/s12891-024-07578-9 -
BMC Musculoskeletal Disorders Jun 2024The aim of this study was to compare the clinical outcomes between patients with chronic ankle instability (CAI) undergoing arthroscopic anterior talofibular ligament... (Comparative Study)
Comparative Study
PURPOSE
The aim of this study was to compare the clinical outcomes between patients with chronic ankle instability (CAI) undergoing arthroscopic anterior talofibular ligament (ATFL) repair who received elastic bandage treatment and those who received lower-leg cast immobilization.
METHODS
CAI patients with isolated ATFL injury undergoing arthroscopic ATFL repair from January 2017 and August 2019 were included in the study. The visual analogue scale (VAS) at rest and during activities, American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (Karlsson score), and time of returning to walk, walk normally, work and sports were evaluated preoperatively, and at 6 months and 12 months follow-up.
RESULTS
A total of 41 patients were included in this study. Among them, 24 patients accepted lower-leg cast fixation, and the other 17 patients were immobilized with elastic bandage. Compared to patients with lower-leg immobilization, patients with elastic bandage fixation had significantly lower VAS during activities (P = 0.021) and higher AOFAS score (P = 0.015) at 12 months follow-up. The Karlsson score at 6 months follow-up were significantly higher in elastic bandage group than those in lower-leg group (P = 0.011). However, no significant difference was observed in time of returning to walk, work and sports between the two groups.
CONCLUSION
Elastic bandage treatment was better than lower-leg cast immobilization in terms of eliminating pain symptom at 12 months follow-up, and improving ankle functional outcome at 6 months follow-up. Moreover, the present study emphasized that lower-leg cast immobilization offered no advantages in arthroscopic ATFL repair postoperative immobilization.
STUDY DESIGN
Cohort study; Level of evidence, 3.
Topics: Humans; Female; Male; Casts, Surgical; Adult; Lateral Ligament, Ankle; Treatment Outcome; Joint Instability; Young Adult; Ankle Joint; Arthroscopy; Retrospective Studies; Ankle Injuries; Immobilization; Middle Aged; Recovery of Function; Follow-Up Studies
PubMed: 38879465
DOI: 10.1186/s12891-024-07584-x -
BMC Surgery Jun 2024We describe a surgical technique for ACL reconstruction combined with anterolateral structure reinforcement and report early clinical follow-up results.
PURPOSE
We describe a surgical technique for ACL reconstruction combined with anterolateral structure reinforcement and report early clinical follow-up results.
METHODS
The semitendinosus and gracilis tendons are braided into 5 strands and the ACL femoral tunnel and tibial tunnel are created. The graft is passed through the tunnel with the use of a traction suture and the tibial end is fixed with absorbable interference screws at 30° of knee flexion. The ACL graft traction suture is used as an anterolateral reconstruction structure to pass through the proximal exit of the ACL femoral tunnel and then through the depth of the iliotibial bundle to the anterior to Gerdy's tubercle, a bony tunnel is created from the anterior to Gerdy's tubercle to the goose foot, and the traction suture is passed through this bony tunnel to form a Loop structure at 20° of knee flexion. Between March 2021 and May 2022 IKDC score, Lysholm score, and Tegner score were performed preoperatively and 6-12 months postoperatively in 24 consecutive patients who met the indications for this procedure and underwent surgery. The patient's maximum flexion angle, the circumference of the thigh, and the stress X-ray between the operated and healthy knee were measured.
RESULTS
Patients showed significant improvement in IKDC score, Lysholm score and Tegner score at a mean follow-up of 7 months postoperatively compared to preoperatively. No significant increase in anterior tibial displacement was found between the patient's operated side and the healthy side.
CONCLUSION
The Loop technique ACLR combined with ALSA can be used in patients with an ACL tear combined with a high degree of positive pivot shift. The patient's subjective perception was significantly improved from the preoperative period and knee stability was restored.
LEVEL OF EVIDENCE
IV, therapeutic study.
Topics: Humans; Anterior Cruciate Ligament Reconstruction; Adult; Male; Female; Anterior Cruciate Ligament Injuries; Treatment Outcome; Young Adult; Follow-Up Studies; Suture Techniques; Range of Motion, Articular; Middle Aged; Tendons; Tibia; Adolescent
PubMed: 38877438
DOI: 10.1186/s12893-024-02439-7 -
Scientific Reports Jun 2024Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as...
Knee osteoarthritis (OA) and obesity are major public health concerns that are closely intertwined. This intimate relationship was documented by considering obesity as the most significant preventable risk factor associated with knee OA. To date, however, the effects of obesity on the knee joint's passive-active structure and cartilage loading have been inconclusive. Hence, this study investigates the intricate relationship between obesity and knee OA, centering on the biomechanical changes in knee joint active and passive reactions during the stance phase of gait. Using a subject-specific musculoskeletal and finite element approach, muscle forces, ligament stresses, and articular cartilage contact stresses were analyzed among 60 individuals with different body mass indices (BMI) classified under healthy weight, overweight, and obese categories. Our predicted results showed that obesity significantly influenced knee joint mechanical reaction, increasing muscle activations, ligament loading, and articular cartilage contact stresses, particularly during key instances of the gait cycle-first and second peak loading instances. The study underscores the critical role of excessive body weight in exacerbating knee joint stress distribution and cartilage damage. Hence, the insights gained provide a valuable biomechanical perspective on the interaction between body weight and knee joint health, offering a clinical utility in assessing the risks associated with obesity and knee OA.
Topics: Humans; Knee Joint; Biomechanical Phenomena; Finite Element Analysis; Body Weight; Obesity; Osteoarthritis, Knee; Male; Gait; Female; Cartilage, Articular; Adult; Body Mass Index; Middle Aged
PubMed: 38877075
DOI: 10.1038/s41598-024-63745-x -
Osteoarthritis and Cartilage Jun 2024Osteoarthritis (OA) prevalence and incidence varies between women and men, but it is unknown whether this follows sex-specific differences in systemic factors (e.g....
OBJECTIVE
Osteoarthritis (OA) prevalence and incidence varies between women and men, but it is unknown whether this follows sex-specific differences in systemic factors (e.g. hormones) and/or differences in pre-morbid joint anatomy. We recognize that classifications of sex within humans cannot be reduced to female/male, but given the lack of literature on non-binary individuals, this review is limited to the sexual dimorphism of articular morphotypes.
METHODS
Based on a Pubmed search using relevant terms, and input from experts, we selected articles based on the authors' judgment of their relevance, interest, originality, and scientific quality; no "hard" bibliometric measures were used to evaluate their quality or importance. Focus was on clinical rather than pre-clinical studies, with most (imaging) data being available for the knee joint.
RESULTS
After introducing "sexual dimorphism", the specific literature on articular morphotypes is reviewed, structured by: radiographic joint space width (JSW), meniscus, ligaments, articular cartilage morphology, articular cartilage composition and deformation, and articular tissue response to treatment.
CONCLUSIONS
Sex-specific differences were clearly observed for JSW, meniscus damage, ligament size, and cartilage morphometry (volume, thickness, and surface areas) but not for cartilage composition. Ligament and cartilage measures were smaller in women even after matching for confounders. Taken together, the findings indicate that female (knee) joints may be structurally more vulnerable and at greater risk of OA. The "one size/sex fits all" approach must be abandoned in OA research, and all observational and interventional studies should report their results for sex-specific strata, at least in pre-specified secondary or post-hoc analyses.
PubMed: 38871022
DOI: 10.1016/j.joca.2024.05.014 -
Journal of Orthopaedic Translation May 2024SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and...
OBJECTIVES
SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and experiments.
METHODS
Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway.
RESULTS
SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11-7082.
CONCLUSION
SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.
PubMed: 38867741
DOI: 10.1016/j.jot.2024.02.009 -
Cureus May 2024Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation...
Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation can be volar or dorsal and closed reduction is rarely successful owing to soft tissue contractures. Treatment options in literature reviews for such rare injuries included open reduction of pip joint with volar plate arthroplasty, extension block pinning, hemi hamate arthroplasty, pip joint arthrodesis, Suzuki dynamic frame fixation, open reduction and repair of capsule and collateral ligaments with suture anchors. Few cases of amputation following treatment were even reported in literature emphasizing the role of meticulous soft tissue handling in such neglected cases of hand. We report six cases of neglected (more than three months old) dorsal dislocation of the PIP joint of the hand, treated with volar plate arthroplasty and extension block pinning. A functional range of motion with a stable joint can be achieved in such injuries with volar plate arthroplasty, as long as the articular cartilage is relatively preserved and bone loss is <30%.
PubMed: 38860079
DOI: 10.7759/cureus.60077 -
Regenerative Therapy Jun 2024Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to...
INTRODUCTION
Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin.
METHODS
In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 10 DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of , and under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of and were evaluated.
RESULTS
Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as , , and , under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of and in synovial fibroblasts.
CONCLUSIONS
The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment.
PubMed: 38859891
DOI: 10.1016/j.reth.2024.05.006 -
Diagnostic and Interventional Radiology... Jun 2024Imaging plays a key role in the diagnosis and management of rheumatic diseases. Although joints and periarticular tissue are commonly involved in rheumatic diseases,...
Imaging plays a key role in the diagnosis and management of rheumatic diseases. Although joints and periarticular tissue are commonly involved in rheumatic diseases, entheses further away from joints, such as in the Achilles tendon or plantar fascia insertion onto the calcaneus, as well as skin and subcutaneous tissue, are among other -sometimes overlooked- targets. The link of enthesitis, which describes inflammation at the insertions of ligaments, tendons, or joint capsules, with spondyloarthritis (SpA) was established just before the turn of the century as a characteristic feature based on imaging studies with histopathological correspondence. To highlight the association between enthesitis and synovitis in SpA, the anatomical unit of the "synovioentheseal complex" (SEC) and the concepts of "functional enthesis" and "articular enthesis," apart from the better known "insertional enthesis," were introduced to encompass other inflammatory lesions associated with SpA. Studies from the last two decades revealed the involvement of the SEC in rheumatic and non-rheumatic disorders with different pathogeneses. Although such involvement is sometimes distinctive, it does not necessarily point to a specific diagnosis at other times. Nevertheless, the potential of SEC inflammation in the differentiation of SpA from other forms of arthritis remains important. The purpose of this review was to provide essential information concerning the involvement of the SEC in the diagnosis of rheumatic diseases and arthritis, focusing on imaging characteristics.
PubMed: 38856322
DOI: 10.4274/dir.2024.242740