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Aberrant activation of the Wnt/β-catenin signaling pathway promotes the progression of osteoarthritis (OA). We previously reported that R-spondin 2 (Rspo2), an activator of the Wnt/β-catenin signaling, facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification. However, the role of Rspo2 in OA remains elusive. Here, we showed that the amounts of Rspo2 protein in synovial fluid were increased in OA patients. We searched for a preapproved drug that suppresses Rspo2-induced Wnt/β-catenin signaling in chondrogenic cells and reduces joint pathology in a rat model of OA. In Rspo2-treated ATDC5 cells, mianserin, a tetracyclic antidepressant, inhibited Wnt/β-catenin signaling, increased proteoglycan production, and upregulated chondrogenic marker genes. Mianserin suppressed Rspo2-induced accumulation of β-catenin and phosphorylation of Lrp6. We identified that mianserin blocked binding of Rspo2 to its receptor Lgr5. We also observed that intraarticular administration of mianserin suppressed β-catenin accumulation and prevented OA progression in a rat model of OA. We conclude that mianserin suppresses abnormally activated Wnt/β-catenin signaling in OA by inhibiting binding of Rspo2 to Lgr5.

The 15 year outcomes after TRO for ONFH are unfavorable because osteoarthritic changes occur after five years post-operatively. Cite this article: Bone Joint J 2017;99-B:175-83.

Postoperative intact ratio <33.3 % and CE angle <25° were identified as independent factors determining radiographic failure and conversion to THA. Therefore, these factors must be taken into consideration when selecting patients for CVO.

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Background: Accelerometer-based portable navigation systems in supine total hip arthroplasty (THA) have been developed, but there are no reports on the accuracy of cup placement. We aimed to investigate and compare the accuracy of the accelerometer-based portable navigation system versus the acetabular alignment guide placed on the pelvis in THA using the direct anterior approach (DAA). Both devices tracked changes in the pelvic position. Methods: In this single-centre, retrospective study, we reviewed 115 hips in 113 patients who underwent primary THA via the DAA using an accelerometer-based portable navigation system in the supine position (portable navigation group) and 106 hips in 101 patients who underwent THA using an acetabular alignment guide (alignment guide group) as controls. Hips were evaluated postoperatively using computed tomography to measure cup orientation. The accuracy of cup orientation was compared between the 2 groups. Results: Absolute values of inclination error were 3.1° ± 2.2° and 2.9° ± 2.3° ( p = 0.708) in the portable navigation and alignment guide groups and those of anteversion error were 2.8° ± 2.3° and 3.7° ± 2.7°, respectively ( p = 0.005). The number of cups placed within 10° of error was 98.3% and 96.2% in the portable navigation and alignment guide groups, respectively ( p = 0.304). The portable navigation group had significantly more hips (72.2%) placed within a 5° margin of error than did the alignment guide group (56.6%) ( p = 0.016). Conclusion: High accuracy in cup placement was achieved using accelerometer-based portable navigation in supine THA. Using a navigation system may contribute to improved long-term outcomes.

The purpose of this study is to investigate the morphometric changes of the subchondral bone during the development of osteoarthritis (OA) in transgenic mice with achondroplasia (Fgfr3 ach ) carrying a heterozygous gain-of-function mutation in Fgfr3. Two OA models (spontaneously developed with age: The aging model, and surgically induced by destabilization of the medial meniscus: The DMM model) were established. Articular cartilage, epiphysis, and metaphysis of the knee joint were histologically and morphometrically compared between wild-type mice, and Fgfr3 ach mice in both OA models. Articular cartilage degeneration was scored according to the Osteoarthritis Research Society International (OARSI) scoring system. Several morphometric parameters including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and subchondral bone thickness in the medial tibial plateau (MTP) (Sb.Th med) were quantified by micro-computed tomography (CT). In the aging model, although there were no significant differences in the OARSI score between wild-type mice and Fgfr3 ach mice, Sb.Th med and Tb.Th in the epiphysis significantly increased in wild-type mice. In the DMM model, the OARSI score of the medial compartment was significantly lower in Fgfr3 ach mice than in wild-type mice. BMD, BV/TV, and Tb.Th in the epiphysis increased in wild-type mice and unchanged in Fgfr3 ach mice, and the Sb.Th med was significantly larger in wild-type mice after surgery. Subchondral sclerosis, which preceded the cartilage degeneration, was inhibited in Fgfr3 ach mice. Activated FGFR3 signaling prevented sclerotic changes of the subchondral bone and subsequent cartilage degeneration. ß