Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by human articular chondrocytes.

OBJECTIVE: To investigate whether janus kinase (JAK) inhibitor exhibits a chondro-protective effect against mechanical stress-induced expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinase (MMPs) in human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were seeded onto stretch chambers and incubated with or without tofacitinib (1000 nM) for 12 h before mechanical stimulation or cytokine stimulation. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 10% elongation, 30 min) was applied and the gene expression levels of type II collagen α1 chain (COL2A1), aggrecan (ACAN), ADAMTS4, ADAMTS5, MMP13, and runt-related transcription factor 2 (RUNX-2) were examined by real-time polymerase chain reaction. Nuclear translocation of RUNX-2 and nuclear factor-κB (NF-κB) was examined by immunocytochemistry, and phosphorylation of mitogen-activated protein kinase (MAPK) and signaling transducer and activator of transcription (STAT) 3 was examined by western blotting. The concentration of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the supernatant was examined by enzyme-linked immunosorbent assay. RESULTS: COL2A1 and ACAN gene expression levels were decreased by CTS, but these catabolic effects were canceled by tofacitinib. Tofacitinib significantly down-regulated CTS-induced expression of ADAMTS4, ADAMTS5, MMP13, and RUNX2, and the release of IL-6 in supernatant by chondrocytes. Tofacitinib also reduced CTS-induced nuclear translocation of RUNX-2 and NF-κB, and phosphorylation of MAPK and STAT3. CONCLUSION: Tofacitinib suppressed mechanical stress-induced expression of ADAMTS4, ADAMTS5, and MMP13 by human chondrocytes through inhibition of the JAK/STAT and MAPK cascades.

Results of Total Elbow Arthroplasty with Cementless Implantation of an Alumina Ceramic Elbow Prosthesis for Patients with Rheumatoid Arthritis.

We investigated the long-term clinical results of total elbow arthroplasty (TEA) by cementless fixation of alumina ceramic unlinked elbow prostheses (J-alumina ceramic elbows: JACE) for the reconstruction of elbow joints with rheumatoid arthritis (RA). Seventeen elbows in 17 patients (aged 44-72 years, average 54.8) replaced by JACE TEA without bone cement were investigated. The average follow-up period was 10.7 (range, 1.0-19.3) years. Clinical conditions of each elbow before and after surgery were assessed according to the Mayo Elbow Performance Index (MEPI). Radiographic loosening was defined as a progressive radiolucent line of more than 1 mm that was completely circumferential around the intramedullary stem. The average MEPI significantly improved from 46.8 points preoperatively to 66.8 points at final follow-up (p=0.0226). However, aseptic loosening was noted in 10 of 17 elbows (58.8%) and revision surgery was required in 7 (41.2%). Most loosening was observed on the humeral side. With radiographic loosening and revision surgery defined as the end points, the likelihoods of prosthesis survival were 41.2% and 51.8%, respectively, up to 15 years by Kaplan-Meier analysis. The clinical results of JACE implantation without bone cement were disappointing, with high revision and loosening rates of the humeral component.

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients.

OBJECTIVE: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. METHODS: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. RESULTS: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436-11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p = 0.029) were associated with an increased risk of DWH. CONCLUSIONS: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.

Hyaluronan suppresses mechanical stress-induced expression of catabolic enzymes by human chondrocytes via inhibition of IL-1ß production and subsequent NF-κB activation.

OBJECTIVE: To investigate the inhibitory effect of hyaluronan (HA) on mechanical stress- induced expression of a disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)-4, -5 and matrix metalloproteinase (MMP)-13 by human chondrocytes. MATERIALS AND METHODS: Normal human articular chondrocytes were pre-incubated with or without 1.0 mg/mL HA (2700 kDa) for 12 h at 37 °C in stretch chambers, then they were exposed to uni-axial cyclic tensile strain (CTS, 0.5 Hz, 10% elongation). The expression of ADAMTS-4, -5, and MMP-13 were analyzed by real-time polymerase chain reaction and Immunocytochemistry. The concentration of IL-1ß in the supernatant was measured using enzyme-linked immunosorbent assay (ELISA). The nuclear translocation of runt-related transcription factor 2 (RUNX-2) and nuclear factor-κB (NF-κB) was examined by ELISA and immunocytochemistry, and phosphorylation of NF-κB was examined by western blotting. RESULTS: HA inhibited mRNA expression of ADAMTS-4, -5, and MMP13 after 24 h CTS via inhibition of IL-1ß secretion and NF-κB activation. However, HA failed to inhibit CTS-induced RUNX-2 expression and subsequent expression of ADAMTS-5 and MMP-13 1 h after CTS. CONCLUSIONS: Our results demonstrated that HA significantly suppressed mechanical stress-induced expression of catabolic proteases by inhibition of the NF-κB-IL-1ß pathway, but did not suppress mechanical stress-induced RUNX-2 signaling.

Short-term results of the PROSNAP linked elbow prosthesis with a snap-in structure and modular flange for the reconstruction of severely damaged rheumatoid elbows.

BACKGROUND: We aimed to evaluate the early clinical results of the reconstruction of problematic elbow joints due to rheumatoid arthritis (RA) using a PROSNAP linked elbow prosthesis (Kyocera Medical, Osaka, Japan) for total elbow arthroplasty. METHODS: Seventeen elbows in 14 RA patients were replaced with a PROSNAP elbow with cement fixation. The patients comprised 1 man and 13 women, with a mean age of 63.9 years (range, 52-83 years) at the time of surgery. The preoperative conditions of the elbows were arthritis mutilans (n = 10), an ankylosed or stiff elbow with a preoperative range of motion of 45° or less (n = 4), and loosening of a primary total elbow arthroplasty (n = 3). The mean follow-up period was 47.7 months (range, 32-69 months), with a 100% follow-up rate. The clinical outcome of the elbows was evaluated by the Mayo Elbow Performance Index (maximum, 100 points). RESULTS: The mean postoperative Mayo Elbow Performance Index score improved from 57.6 points to 97.1 points. Preoperatively, 3 of the 17 elbows were judged as good, 7 as fair, and 7 as poor; at final follow-up, 16 elbows were judged as excellent and 1 as good. Complications were noted in 1 elbow (6%), which had undergone a postoperative fracture. CONCLUSIONS: The PROSNAP elbow prosthesis can be safely implanted through a relatively easy procedure and provides satisfactory short-term clinical outcomes for the reconstruction of severely damaged RA elbows. LEVEL OF EVIDENCE: Level IV, case series, treatment study.

Postoperative clinical outcomes of unicompartmental knee arthroplasty in patients with isolated medial compartmental osteoarthritis following medial meniscus posterior root tear.

BACKGROUND: Cartilage degradation progresses rapidly following medial meniscus posterior root tear (MMPRT). Unicompartmental knee arthroplasty (UKA) has been performed for medial compartmental osteoarthritis following MMPRT. We evaluated the clinical and radiographic outcomes of UKA for medial compartmental osteoarthritis after an untreated MMPRT. METHODS: Twenty-one patients who underwent UKA for isolated medial compartment osteoarthritis following MMPRT were retrospectively investigated. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score and knee range of motion. The posterior tibial slope and tibial component inclination were evaluated using plain radiographs. RESULTS: The mean follow-up periods were 25.5 ± 13.8 months. Clinical outcomes improved significantly postoperatively. The mean postoperative knee extension angle was -1.1° ± 2.1°, and the knee flexion angle was 134.3° ± 4.9°. The posterior tibial slope angle decreased from 9.0° ± 2.0° preoperatively to 5.4° ± 1.8° postoperatively, and postoperative tibial component inclination at the final follow-up was 2.9° ± 1.1° varus. No aseptic loosening or deep infections were observed. CONCLUSION: UKA significantly improved clinical outcomes and could be a viable surgical option for treating isolated medial compartmental osteoarthritis accompanied by untreated MMPRT.