Chondromodulin is necessary for cartilage callus distraction in mice

Abstract

Chondromodulin (Cnmd) is a glycoprotein known to stimulate chondrocyte growth. We examined in this study the expression and functional role ofCnmdduring distraction osteogenesis that is modulated by mechanical forces. The right tibiae of the mice were separated by osteotomy and subjected to slow progressive distraction using an external fixator.In situhybridization and immunohistochemical analyses of the lengthened segment revealed thatCnmdmRNA and its protein in wild-type mice were localized in the cartilage callus, which was initially generated in the lag phase and was lengthened gradually during the distraction phase. InCnmdnull (Cnmd−/−) mice, less cartilage callus was observed, and the distraction gap was filled by fibrous tissues. Additionally, radiological and histological investigations demonstrated delayed bone consolidation and remodeling of the lengthened segment inCnmd−/−mice. Eventually,Cnmddeficiency caused a one-week delay in the peak expression ofVEGF,MMP2, andMMP9genes and the subsequent angiogenesis and osteoclastogenesis. We conclude that Cnmd is necessary for cartilage callus distraction.