A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair

Annals of the New York Academy of Sciences
Bhavita WaliaHicham Drissi

Abstract

Osteoporosis management is currently centered around bisphosphonates, which inhibit osteoclast (OC) bone resorption but do not affect bone formation. This reduces fracture risk, but fails to restore healthy bone remodeling. Studies in animal models showed that cathepsin K (CatK) inhibition by genetic deletion or chemical inhibitors maintained bone formation while abrogating resorption during bone remodeling and stimulated periosteal bone modeling. Recently, periosteal mononuclear tartrate-resistant acid phosphatase-positive (TRAP+ ) osteoclast precursors (OCPs) were shown to augment angiogenesis-coupled osteogenesis. CatK gene deletion increased osteoblast differentiation via enhanced OCP and OC secretion of platelet-derived growth factor (PDGF)-BB and sphingosine 1 phosphate. The effects of periosteum-derived OCPs on bone remodeling are unknown, particularly with regard to fracture repair. We hypothesized that periosteal OCPs derived from CatK-null (Ctsk-/- ) mice may enhance periosteal bone formation during fracture repair. We found fewer periosteal OCPs in Ctsk-/- mice under homeostatic conditions; however, after fracture, this population increased in number relative to that seen in wild-type (WT) mice. Enhanced TRAP stainin...Continue Reading

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Citations

Aug 8, 2021·International Journal of Molecular Sciences·Yongguang GaoJingxian Jia
Oct 19, 2021·Frontiers in Pharmacology·Juan DuanZhengxiao Ouyang

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