The role of the SIBLING, Bone Sialoprotein in skeletal biology — Contribution of mouse experimental genetics

• Bone Sialoprotein (BSP) is an extracellular matrix Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING)
• BSP gene knockout (-/-) and overexpression mouse models brought major clues to understand the role of BSP in bone
• Lack of BSP affects mineralization, bone cell differentiation and activity, haematopoiesis and bone vascularization
• BSP-/- mice overexpress another SIBLING, Osteopontin (OPN)
• OPN could induce some aspects of the BSP-/- skeletal phenotype, while replacing BSP for some of its functions

Bone Sialoprotein (BSP) is a member of the “Small Integrin-Binding Ligand N-linked Glycoproteins” (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genetically engineered mice (BSP gene knockout and overexpression) to the understanding of the role of BSP in the bone organ. The studies made so far highlight the role of BSP in skeletal mineralization, as well as its importance for proper osteoblast and osteoclast differentiation and activity, most prominently in primary/repair bone. The absence of BSP also affects the local environment of the bone tissue, in particular hematopoiesis and vascularization. Interestingly, lack of BSP induces an overexpression of OPN, and the cognate protein could be responsible for some aspects of the BSP gene knockout skeletal phenotype, while replacing BSP for some of its functions. Such interplay between the partly overlapping functions of SIBLING proteins, as well as the network of cross-regulations in which they are involved should now be the focus of further work.