Collagen type XII is a member of the fibril-associated collagens with interrupted triple helices (FACIT) group, thought to be bound to the surface of interstitial collagen fibrils (Keene et al.1991). It has only one alpha chain type, with two collagenous (Col1 and Col2) and three noncollagenous domains (NC1-NC3). Whereas the collagenous and the NC1 and NC2 regions are short, the NHE-terminal NC3 is a huge trimeric domain (Yamagata et al. 1991, Wälchli et al. 1993). Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils (Nishiyama et al. 1994, Bader et al. 2009). It may be a stress response molecule, directly influenced by stretch and shear stress. Expression of COL12A1 is directly stimulated by mechanical forces (Flück et al. 2003, Jin et al. 2003, Arai et al. 2008). Expression is predominantly in bone, suggesting involvement of type XII collagen in the regulation of osteoblasts and cell interactions. Transgenic type XII collagen-null mice have skeletal abnormalities. They have decreased bone matrix deposition and delayed maturation. Compared with controls, Col12a knockout osteoblasts are disorganized, being less polarized with disrupted cell-cell interactions, decreased connexin43 expression and impaired gap junction function (Izu et al. 2011).
MMP12 can cleave collagen XII (Didangelos et al. 2011).