Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

Abstract

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (−/−) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP−/− mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (≥12 mo) BSP−/− mice. At 4 mo, BSP−/− mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP−/− versus WT bone marrow stromal cultures. BSP−/− hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP−/− mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN−/− mice.

Increased serum osteopontin is a risk factor for osteoporosis in menopausal women

“…Previous reports have indicated that OPN knockout mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice [19]. The role of OPN in the regulation of bone metabolism has been suggested in many animal studies [2,[19][20][21][22][23][24] However, the association between OPN levels and osteoporosis in humans is still unclear [25]. In this study, we hypothesized that women with high serum OPN levels may show less resistance to postmenopausal osteoporosis.…”

Isoform-specific O-Glycosylation of Osteopontin and Bone Sialoprotein by Polypeptide N-Acetylgalactosaminyltransferase-1

“…Characterization of Bone Sialoprotein and Osteopontin Glycosylation-OPN and BSP are members of the SIBLING family of proteins that are expressed by bone resident cells and play an important role in normal bone development, mineralization, and remodeling (31)(32)(33).…”

Bone cell–matrix protein interactions

“…Bone sialoprotein-deficient mice show decreased bone formation and osteoclastogenesis [68] whereas BSP overexpression enhances osteoblast differentiation in vitro [69]. These findings provide evidence that extracellular matrix components control bone cells and bone remodeling, although the precise mechanisms are not yet fully understood.…”