Efficacy of ADIPOR1 and ADIPOR2 peptide-agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis.

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis.

AdipoRon reduces TGFβ1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells.

Irrigation and Debridement With Chronic Antibiotic Suppression for the Management of Acutely Infected Aseptic Revision Total Joint Arthroplasties.

Background: Most data on irrigation and debridement with component retention (IDCR) as a treatment for acute periprosthetic joint infections (PJIs) focuses on primary total joint arthroplasties (TJAs). However, the incidence of PJI is greater after revisions. We investigated the outcomes of IDCR with suppressive antibiotic therapy (SAT) following aseptic revision TJAs.

The Safety of Adiponectin Receptor Agonist AdipoRon in a Rabbit Model of Arthrofibrosis.

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with numerous reported physiological benefits in murine models of human disease, including a proposed reduction in fibrosis. However, AdipoRon has never been investigated in rabbits, which provide a robust model for orthopedic conditions. We examined the safety of intravenous (IV) AdipoRon in New Zealand White (NZW) female rabbits surgically stressed by a procedure that mimics human arthrofibrosis.

The epigenetic regulator BRD4 is required for myofibroblast differentiation of knee fibroblasts.

Arthrofibrosis, which is characterized by excessive scar tissue and limited motion, can complicate the daily functioning of patients after total knee arthroplasty (TKA). Molecular hallmarks of arthrofibrosis include pathologic accumulation of myofibroblasts and disproportionate collagen deposition. Epigenetic mechanisms, including posttranslation modification of histones, control gene expression and may regulate fibrotic events.

Knee immobilization reproduces key arthrofibrotic phenotypes in mice.

Aims: As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods: Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal.

Immune cell populations differ in patients undergoing revision total knee arthroplasty for arthrofibrosis.

Arthrofibrosis following total knee arthroplasty (TKA) is a debilitating condition typically diagnosed based on clinical findings. To gain insight into the histopathologic immune cell microenvironment of arthrofibrosis, we assessed the extent of tissue fibrosis and quantified immune cell populations in specific tissue regions of the posterior capsule. We investigated specimens from three prospectively-collected, matched cohorts, grouped as patients receiving a primary TKA for osteoarthritis, revision TKA for arthrofibrosis, and revision TKA for non-arthrofibrotic, non-infectious reasons.

The transcription factor RFX5 coordinates antigen-presenting function and resistance to nutrient stress in synovial macrophages.

Tissue macrophages (Mϕ) are essential effector cells in rheumatoid arthritis (RA), contributing to autoimmune tissue inflammation through diverse effector functions. Their arthritogenic potential depends on their proficiency to survive in the glucose-depleted environment of the inflamed joint. Here, we identify a mechanism that links metabolic adaptation to nutrient stress with the efficacy of tissue Mϕ to activate adaptive immunity by presenting antigen to tissue-invading T cells.

Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation.

Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee-related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options.

Outcomes of primary total hip arthroplasty following septic arthritis of the hip : a case-control study.

Aims: Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA.

Methods: We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution.

Outcomes of Primary Total Knee Arthroplasty Following Septic Arthritis of the Native Knee: A Case-Control Study.

Background: Septic arthritis of the native knee often results in irreversible joint damage leading to the need for total knee arthroplasty (TKA). The purpose of the present study was to examine the intermediate-term risk of periprosthetic joint infection (PJI), aseptic revision, and reoperation following primary TKA in patients with a history of septic arthritis of the native knee as compared with primary TKA performed for the treatment of osteoarthritis.

Methods: We retrospectively identified 215 primary TKAs performed from 1971 to 2016 at a single institution in patients with a history of septic arthritis of the native knee.

Biomechanical, histological, and molecular characterization of a new posttraumatic model of arthrofibrosis in rats.

Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats.

A Potential Theragnostic Regulatory Axis for Arthrofibrosis Involving Adiponectin (ADIPOQ) Receptor 1 and 2 (ADIPOR1 and ADIPOR2), TGFβ1, and Smooth Muscle α-Actin (ACTA2).

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin () as a potential candidate.

Anti-fibrotic effects of the antihistamine ketotifen in a rabbit model of arthrofibrosis.

Aims: Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

Methods: A group of 12 skeletally mature rabbits were randomly divided into two groups.

Total Protein Staining is Superior to Classical or Tissue-Specific Protein Staining for Standardization of Protein Biomarkers in Heterogeneous Tissue Samples.

Protein detection techniques such as western blotting and ELISA rely on housekeeping proteins as standards for sample normalization. However, clinical or animal tissue specimens are heterogeneous due to presence of contaminating cell types and tissues (e.g.

Molecular pathology of human knee arthrofibrosis defined by RNA sequencing.

Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA).