In vivo mouse model of calcific myonecrosis induced by injury.

Skeletal muscle is the major tissue that provides a space and source for bone, which is formed by osteoblasts through the secretion of extracellular matrices, such as type I collagen, and the deposition of hydroxyapatite calcium phosphate crystals. In the present study, we injected notexin, a snake venom, into skeletal muscle to induce local injury. Notexin injection caused local ectopic calcification in muscle fibers within a couple of days, which remained for more than 16 months. In contrast to ectopic bone formation, the damaged muscles after injection of notexin contains neither bone marrow cells, osteoblasts, nor osteoclasts. Histological and chemical analyses of the notexin-induced calcified objects revealed the deposition of stable hydroxyapatite crystals in muscle fibers, which was distinct from ectopic bone formation. We conclude that this in vivo mouse model of calcific myonecrosis induced by injury is useful for studying the molecular mechanisms of and potential therapeutics for calcific myonecrosis.