Fetuin inhibition of heterotopic ossification in vitro

Abstract

Introduction: Heterotopic bone or ossification (HO) refers to the formation of osseous tissue at a location other than where it would normally be found, and can also be referred to as being ectopic bone. Fully differentiated osseous tissue forms at a location where bone was not meant to be. When such bone forms in following total or sub-total joint replacement surgery, a variety of complications can occur including dramatic reductions in joint function leading to marked restriction of movement to complete ankylosis (ie, total loss of movement). Small case series have demonstrated that HO may develop in as many as 35% of TMJ reconstruction cases. Although the pathophysiology of HO is not well understood, it has been suggested that primitive mesenchymal cells near surgical sites where bone surgery may have been done are exposed to residual bone dust, the latter containing bone morphogenetic proteins (BMP), cytokines that induce osteodifferentiation in mesenchymal cells hence leading to osteogenesis. Fetuin, also known as a2HS-glycoprotein (Ahsg), is a serum and bone resident glycoprotein, which binds TGFb and BMP cytokines due to the fact that it has a BMP/TGFb receptor-like region within its structure. Ahsg inhibits TGFb-induced in vitro osteogenesis, most likely by acting as a decoy receptor for TGFb and BMP. Given this, we hypothesized that fetuin would inhibit BMP mediated effects in cell culture and ultimately in vivo.