The Wnt serpentine receptor Frizzled-9 regulates new bone formation in fracture healing.

摘要: Wnt signaling is a key regulator of bone metabolism and fracture healing. The canonical Wnt/β-catenin pathway regarded as the dominant mechanism, targeting this has emerged promising strategy for treatment osteoporosis poorly healing fractures. In contrast, little known about role non-canonical in bone. Recently, it was demonstrated that serpentine receptor Fzd9, Frizzled family, essential osteoblast function positively regulates remodeling via without involving β-catenin-dependent signaling. Here we investigated whether Fzd9 using femur osteotomy model Fzd9(-/-) mice. After 10, 24 32 days calli were analyzed biomechanical testing, histomorphometry, immunohistochemistry, micro-computed tomography. Our results significantly reduced amounts newly formed at all time points absence and, accordingly, decreased mechanical competence callus tissue late phase cartilage formation numbers osteoclasts degrading mineralized matrix unaltered. β-Catenin immunolocalization showed Wnt-signaling not affected osteoblasts well proliferating mature chondrocytes within callus. expression established differentiation markers altered whereas chemokines Ccl2 Cxcl5 seemed to be reduced. Collectively, our suggest intramembranous endochondral during healing, does participate or osteoclastic degradation matrix. finding addition its physiological remodeling, repair may have implications development treatments non-healing