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A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair
Author(s) -
Walia Bhavita,
Lingenheld Elizabeth,
Duong Le,
Sanjay Archana,
Drissi Hicham
Publication year - 2018
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13629
Subject(s) - cathepsin k , osteoclast , bone resorption , bone healing , bone remodeling , medicine , endocrinology , chemistry , periosteum , tartrate resistant acid phosphatase , cathepsin , osteoporosis , osteoblast , resorption , microbiology and biotechnology , biology , anatomy , biochemistry , receptor , in vitro , enzyme
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 staining and greater expression of PDGF‐BB were observed in fractured Ctsk –/– femurs relative to WT femurs. This early pattern of augmented PDGF‐BB expression in Ctsk –/– mice may contribute to improved fracture healing by enhancing callus mineralization in Ctsk –/– mice.