ARID5B is a negative modulator of IL-6 production in rheumatoid arthritis synovial fibroblasts.

Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including ARID5B, a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-α in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-α. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the ARID5B gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-α. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of ARID5B intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.

Effect of hardware removal and second-look arthroscopy after open-wedge high tibial osteotomy.

INTRODUCTION: Open-wedge high tibial osteotomy (OWHTO) is the standard and safe procedure for medial compartment osteoarthritis. Although hardware removal (HWR) is performed after post-OWHTO bone union, the effects of HWR on OWHTO have been rarely reported. We hypothesised that HWR would improve range of motion (ROM) and implant-related complications. Thus, this study aimed to investigate the effects of HWR on postoperative ROM, the Japan Orthopaedic Association (JOA) score/visual analogue scale (VAS) score and hardware-related complications after OWHTO. METHODS: Patients who underwent OWHTO between January 2016 and June 2018 and HWR were retrospectively reviewed. To perform OWHTO, locking plates and prosthetic bone were used to achieve optimal stabilisation of biplanar osteotomy. HWR was performed after a second-look arthroscopy through the previous skin incision. For clinical evaluation, the JOA score, VAS score, and ROM were assessed before and 1 year after HWR using the Wilcoxon rank test. Logistic regression analysis was performed to identify the predictors of post-HWR improvement. RESULTS: Of 98 knees examined (91 patients), 80 (73 patients; 39 men and 34 women) were included. At the time of OWHTO, mean age was 64.0 ± 9.7 years and body mass index, 25.5 ± 3.1 kg/m2; Kellgren-Lawrence (KL) grade 1 was seen in 20 cases, KL-2 in 46, and KL-3 in 14. Mean periods between OWHTO and HWR were 13.4 ± 2.0 months, and 11.9 ± 1.2 months between HWR and evaluation. The JOA score and flexion angle significantly improved after HWR (The JOA score: p = 0.026 flexion angle: p < 0.001); however, the VAS score and extension angle did not (VAS score: p = 0.162, extension angle: p = 0.934). Hardware irritation was observed in four cases (5%), which improved after HWR. Logistic regression analysis revealed that lower preoperative KL grade and flexion angle were predictors of improvement after HWR [KL grade: p = 0.008; odds ratio 3.244, 95% confidence interval (CI) 1.350-7.794; flexion angle: p < 0.001; odds ratio 1.150, 95% CI 1.062-1.245]. CONCLUSION: HWR improves flexion angle, clinical outcomes and hardware-related complications after OWHTO. Preoperative KL grade and flexion angle are predictors of improvement after HWR in patients who have undergone OWHTO.

Good clinical outcomes and return to sports after hybrid closed-wedge high tibial osteotomy.

PURPOSE: This study aimed to investigate preoperative sports participation and postoperative clinical outcomes including a return to sports (RTS) after hybrid closed-wedge high tibial osteotomy (CWHTO) for medial compartment osteoarthritis of the knee. Characteristic of Hybrid CWHTO was defined as extra-articular lateral closed and medial open wedge osteotomy. METHODS: The patients who underwent hybrid CWHTO from January 2016 to December 2018 were retrospectively reviewed and divided them into sports and non-sports groups. The preoperative demographic and radiographic characteristics were compared in both groups. And the clinical outcomes including the Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), Lysholm score, University of California at Los Angeles (UCLA) activity score, and RTS in the sports group were also investigated. Statistical analysis was performed for comparisons among the preoperative factors between the two groups. Influence of sports impact and bone union of fibular osteotomy was also statistically investigated for RTS. RESULTS: Of the 161 knees (129 patients; 46 males, 83 females), 20 knees (16 patients; 13 males, 3 females; 12.3%) belonged to sports group. Although there were no significant differences regarding the age and radiographic parameters, there were significant differences in the body mass index and proportion of males between both groups. The JOA, VAS, Lysholm, and UCLA activity scores significantly improved after surgery. RTS was 80% at a mean duration of 7.2 ± 3.1 months. RTS in the high-impact sports group was significantly lower than that in the low-impact sports group (high-impact 60% vs. low-impact 100%, p = 0.043). There was no significant difference in RTS regarding bone union after fibular osteotomy. CONCLUSION: The clinical outcomes including RTS were satisfactory in patients with hybrid CWHTO. LEVEL OF EVIDENCE: IV.

Mid-term results of medial open-wedge high tibial osteotomy based on radiological grading of osteoarthritis.

PURPOSE: To evaluate the mid-term results of medial open-wedge high tibial osteotomy (OWHTO) based on Kellgren-Lawrence (KL) grades. MATERIALS AND METHODS: We retrospectively evaluated clinical and radiographic outcomes of 93 patients (mean age 61.4 years, mean follow-up 64.2 months, 109 consecutive knees) who underwent OWHTO for medial compartment osteoarthritis (OA). KL grade was used to evaluate knee OA (KL-1 22 cases; KL-2, 51 cases; KL-3, 36 cases). The clinical outcomes were assessed using Japanese Orthopaedic Association (JOA) and Lysholm scores. Radiographic outcomes were assessed using pre- and post-operative mechanical axis percentage, femorotibial angle, medial proximal tibial angle, and joint line convergence angle. Hinge fracture frequency and OA progression were also evaluated based on KL grades. RESULTS: The JOA score improved significantly from 70.3 ± 14.9 to 96.2 ± 4.4, 64.1 ± 12.5 to 95.1 ± 5.1, and 68.6 ± 11.4 to 92.1 ± 6.1 in the KL-1, KL-2, and KL-3 groups, respectively. The JOA score in the KL-3 group was significantly lower than in the other groups. The Lysholm score improved significantly from 62.6 ± 8.8 to 97.7 ± 4.7, 62.1 ± 8.1 to 96.7 ± 4.2, and 59.2 ± 9.2 to 95.8 ± 4.6 in the KL-1, KL-2, and KL-3 groups, respectively. The post-operative Lysholm scores were not significantly different among the groups. There were significant differences in radiographic parameters pre-operatively, but not post-operatively, among the groups. Although there were no significant differences in hinge fracture frequency and OA progression, the KL-3 grade predicted OA progression on multivariate analysis. CONCLUSIONS: Mid-term results of OWHTO significantly improved. However, clinical score in the KL-3 group was lower than that in the KL-1 and KL-2 groups; radiological OA progression was a risk factor in KL-3.

CD34+THY1+ synovial fibroblast subset in arthritic joints has high osteoblastic and chondrogenic potentials in vitro.

OBJECTIVE: Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34+THY1+, CD34-THY1-, and CD34-THY1+. The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function. METHODS: SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs. RESULTS: The expression levels of THY1+, CD73+, and CD271+ were highest and those of CD54+ and CD29+ were lowest in CD34+THY1+ among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34+THY1+ subset. Consistently, the expressions of differentiation markers of the osteoblasts (RUNX2, ALPL, and OCN) or chondrocytes (ACAN) were the highest in the CD34+THY1+ subset, indicating that the CD34+THY1+ subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ. The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker. CONCLUSION: The CD34+THY1+ SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34+THY1+ subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.

Hypermobile Anterior Horn of the Lateral Meniscus: A Case Report and Literature Review.

Hypermobile meniscus is known as one of the causes of knee pain and locking or limitation of the range of motion during knee flexion, even when there is no evidence of meniscus tear on magnetic resonance imaging (MRI). Most such cases show excessive hypermobility of the posterior part of the lateral meniscus. This case report presented a rare case of a hypermobile anterior horn of the lateral meniscus. An 18-year-old woman visited our hospital for left knee pain without trauma. Her physical examination showed a limited range of motion and tenderness in the lateral joint space. However, her MRI did not show any abnormalities. After conservative treatment failed, we performed arthroscopic surgery. The arthroscopic evaluation showed no meniscus and no other intraarticular injury. However, the anterior horn of the lateral meniscus was easily translated beyond the lateral condyle by using a probe. Thus, hypermobile anterior horn of the lateral meniscus was diagnosed. The meniscus was stabilized by the outside-in technique. Immediately after surgery, the catching symptom and pain were alleviated. After three-and-a-half months, she returned to work. The Lysholm score improved from 55, preoperatively, to 100, 1-year postoperatively. In conclusion, careful arthroscopic evaluation is essential for the diagnosis of a hypermobile anterior horn of the lateral meniscus. Arthroscopic meniscus stabilization provides a good outcome for hypermobile meniscus.

Time to Bone Union after Hybrid Closed-Wedge High Tibial Osteotomy.

Medial open- and lateral closed-wedge high tibial osteotomy (hybrid CWHTO) can overcome the limitations of conventional CWHTO and open-wedge HTO (OWHTO) for medial compartmental osteoarthritis (OA) of the knee. Hybrid CWHTO increases stability by using a rigid locking plate and allows early full weight-bearing. However, the literature contains no information about time to bone union after this new procedure. The aim of this study is to evaluate the time to bone union after hybrid CWHTO. We reviewed 44 knees treated with hybrid CWHTO. Patients were able to stand on both legs on the day after surgery and walked with full weight-bearing within 4 weeks of the procedure. The time to achievement of bone union at the osteotomy site was defined as the number of months until bone union was confirmed on radiographic imaging. The mean time to radiographic confirmation of bone union was 4.5±1.5 months after surgery. Eleven knees (25.0%) required 6 months or more. Radiographic analysis and JOA score improved significantly between before and 1 year after surgery (p<0.01). Hybrid CWHTO is a very useful method for treating medial OA, but radiographic bone union requires 4.5 months on average. We must be aware of bone union after hybrid CWHTO.

Two Cases of High Tibial Osteotomy in Patients with Rheumatoid Arthritis Treated with Biologic Disease-modifying Anti-rheumatic Drugs.

High tibial osteotomy (HTO) procedure is generally contraindicated in rheumatoid arthritis (RA) patients because synovial inflammation may exacerbate joint damage post-surgery. The natural course of joint destruction in RA changed dramatically with new treatment strategies and the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs). We report the cases of two RA patients who underwent HTO and whose disease activities were well controlled by bDMARDs. Despite their short follow-up periods, they showed acceptable objective and subjective clinical results. We believe that the combination of bDMARDs and HTO can be indicated for selected RA patients before total knee arthroplasty.

Blood loss in patients for total knee arthroplasty.

Ninety-four patients with osteoarthritis (OA) and 180 with rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA) were analyzed to clarify the necessity for preoperative autogenous blood deposition or homologous blood transfusion. Two hundred and twenty-four and 50 patients underwent TKA with cement and without cement, respectively. The difference in average blood loss in patients between with (372 ml) and without cementation (449 ml) was significant. In the OA group the average blood loss significantly decreased after cementation but not in the RA group. Although the rate of avoiding transfusion in the OA group did not significantly decrease with the use of cement (92.4% vs. 93.3%), that in the RA group did (80% to 57.1%). Eight of 159 patients with hemoglobin level (Hb) of 11.0 g/dl or higher received homologous blood transfusion. Of these eight patients five had associated disorders. Only one patient with Hb of 12.0 g/dl or higher underwent homologous blood transfusion. Patients with Hb of 12.0 g/dl or higher are not indicated for preoperative autologous blood deposition. In patients with Hb between 11.0 and 12.0 g/dl preoperative blood deposition may be planned after consideration of general condition and complication. Patients with Hb lower than 11.0 g/dl should undergo preoperative blood deposition.