Model for role of type XII collagen in osteoblast development and bone formation. Type XII collagen surrounding immature osteoblasts responds to mechanical stimuli that initiate osteoblast maturation. This is associated with increased osteoblast organization, cell–cell interaction, and polarization along bone deposition interfaces. Further localized production of type XII collagen by well-organized polar osteoblasts reinforces the osteoblast organization and maturation. Cell–cell interaction drives Cx43 expression, thereby establishing cell communication via gap junctions, resulting in terminal differentiation, increased bone matrix protein production, and organized deposition of a functional bone matrix. In the absence of type XII collagen, there is a dysfunctional response to the mechanical stimuli and an alteration in the osteoblast maturation sequence. This defect delays/alters osteoblast organization, polarity, and cell–cell contacts, and, therefore, the downstream pathways, including up-regulation of Cx43 and bone matrix proteins, are compromised. Together, this results in decreased bone formation and quality.