Abstract
Osteopontin is an RGDS-containing protein that acts as a ligand for the alpha(v)beta(3) integrin, which is abundantly expressed in osteoclasts, cells responsible for bone resorption in osteopenic diseases such as osteoporosis and hyperparathyroidism. However, the role of osteopontin in the process of bone resorption has not yet been fully understood. Therefore, we investigated the direct function of osteopontin in bone resorption using an organ culture system. The amount of (45)Ca released from the osteopontin-deficient bones was not significantly different from the basal release from wild type bones. However, in contrast to the parathyroid hormone (PTH) enhancement of the (45)Ca release from wild type bones, PTH had no effect on (45)Ca release from organ cultures of osteopontin-deficient bones. Because PTH is located upstream of receptor activator of NF-kappaB ligand (RANKL), that directly promotes bone resorption, we also examined the effect of RANKL. Soluble RANKL with macrophage-colony stimulating factor enhanced (45)Ca release from the bones of wild type fetal mice but not from the bones of osteopontin-deficient mice. To obtain insight into the cellular mechanism underlying the phenomena observed in osteopontin-deficient bone, we investigated the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the bones subjected to PTH treatment in cultures. The number of TRAP-positive cells was increased significantly by PTH in wild type bone; however, no such PTH-induced increase in TRAP-positive cells was observed in osteopontin-deficient bones. These results indicate that the absence of osteopontin suppressed PTH-induced increase in bone resorption via preventing the increase in the number of osteoclasts in the local milieu of bone.
Highlights
Osteoclastic bone resorption is a key event in the pathophysiology of osteopenic diseases such as osteoporosis and hyperparathyroidism
To obtain insight into the cellular mechanism underlying the phenomena observed in osteopontin-deficient bone, we investigated the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the bones subjected to parathyroid hormone (PTH) treatment in cultures
PTH binds to receptors expressed on osteoblasts and/or stromal cells and enhances expression of membrane-bound RANKL, which in turn binds to its receptor, receptor activator of NFB, on osteoclasts or their precursors, to enhance osteoclast development and/or osteoclast activity [35,36,37]
Summary
Osteoclastic bone resorption is a key event in the pathophysiology of osteopenic diseases such as osteoporosis and hyperparathyroidism. Bone matrix consists of about 90% type I collagen and about 5% noncollagenous proteins Among these noncollagenous proteins, at least five proteins, osteopontin, bone sialoprotein, thrombospondin, fibronectin, and vitronectin, contain RGD sequences that can be recognized by some integrins [5,6,7,8]. At least five proteins, osteopontin, bone sialoprotein, thrombospondin, fibronectin, and vitronectin, contain RGD sequences that can be recognized by some integrins [5,6,7,8] These noncollagenous bone proteins are candidate ligands for the ␣v3 integrin expressed on the osteoclasts. To elucidate the mechanism of osteopontin action, we investigated bone resorption in organ cultures in which osteoclastic activity was stimulated by PTH.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
