Sclerostin antibody promotes bone formation through the Wnt/β-catenin signaling pathway in femoral trochlear after patellar instability

Abstract

ABSTRACT Purpose The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab). Materials and Methods We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 µl), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, β-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson’s trichrome staining were performed to evaluate cartilage changes. Results PI increased the expression of SOST/sclerostin and RANKL, and decreased β-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation. Conclusions SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/β-catenin signaling pathway in the femoral trochlear after PI.