Bone Mineralization and Osteoblast Differentiation Are Negatively Modulated by Integrin αvβ3

• Published in: Journal of bone and mineral research Vol. 16; no. 2; pp. 277 - 288
• Main Authors: Cheng, Su‐Li, Lai, Chung‐Fang, Blystone, Scott D., Avioli, Louis V.
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.02.2001; American Society for Bone and Mineral Research
• Subjects: adhesion; Biological and medical sciences; differentiation; Fundamental and applied biological sciences. Psychology; integrin; osteoblasts; proliferation; Skeleton and joints; Vertebrates: osteoarticular system, musculoskeletal system; Cell proliferation; Rodentia; Gene overexpression; Adhesion; Osteoarticular system; Vertebrata; Cell line; Mammalia; Integrin; Mouse; Mineralization; Animal; Osteoblast; Bone; Differentiation
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2001.16.2.277

Numerous bone matrix proteins can interact with αv‐containing integrins including αvβ3. To elucidate the net effects of the interaction between these proteins and αvβ3 on osteoblast function, we developed a murine osteoblastic cell line that overexpressed human αvβ3. Human αvβ3‐integrin was expressed on cell membrane, in which its presence did not alter the surface level of endogenous mouse αvβ3. The expressed human αvβ3 was functional because cell adhesion to osteopontin was increased and this increment was abolished by antibody against human αvβ3. The proliferation rate of cells overexpressing αvβ3 (αvβ3‐cells) was increased whereas matrix mineralization was decreased. To elucidate the mechanisms leading to inhibition of matrix mineralization, the expression of proteins important for mineralization was analyzed. Alkaline phosphatase activity and the expression of osteocalcin, type I collagen, and bone sialoprotein (BSP) were decreased whereas osteopontin was stimulated in αvβ3‐cells. The regulation of osteopontin, osteocalcin, and BSP expression was mediated via transcriptional mechanism because their promoter activities were altered. Examination of molecules involved in integrin signaling indicated that activator protein‐1 (AP‐1) and extracellular signal‐regulated kinase (Erk) activities were enhanced whereas c‐jun N‐terminal kinase (JNK) activity was decreased in αvβ3‐cells. The activity of p38 and the levels of focal adhesion kinase (FAK) and vinculin were not altered. Moreover, the adhesions of αvβ3‐cells to type I collagen and fibronectin were inhibited, which was attributed to decreased β1‐integrin levels on cell surface. In conclusion, overexpressing αvβ3‐integrin in osteoblasts stimulated cell proliferation but retarded differentiation, which were derived via altered integrin‐matrix interactions, signal transduction, and matrix protein expression.