SPARC/osteonectin in mineralized tissue

• The regulation of procollagen processing by SPARC and potential roles in bone matrix assembly
• Functional implications of SPARC in the regulation of collagen cross linking by transglutaminase
• Phenotypic differences characteristic of SPARC-null bones, osteoblasts, and osteoclasts
• SPARC mutations identified in patients with OI and idiopathic osteoporosis
• Functional implications of SPARC in the regulation of collagen crosslinking by transglutaminase

Secreted protein acidic and rich in cysteine (SPARC/osteonectin/BM40) is one of the most abundant non-collagenous protein expressed in mineralized tissues. This review will focus on elucidating functional roles of SPARC in bone formation building upon results from non-mineralized cells and tissues, the phenotype of SPARC-null bones, and recent discoveries of human diseases with either dysregulated expression of SPARC or mutations in the gene encoding SPARC that give rise to bone pathologies. The capacity of SPARC to influence pathways involved in extracellular matrix assembly such as procollagen processing and collagen fibril formation as well as the capacity to influence osteoblast differentiation and osteoclast activity will be addressed. In addition, the potential for SPARC to regulate cross-linking of extracellular matrix proteins by members of the transglutaminase family of enzymes is explored. Elucidating defined biological functions of SPARC in terms of bone formation and turnover are critical. Further insight into specific cellular mechanisms involved in the formation and homeostasis of mineralized tissues will lead to a better understanding of disease progression.