Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells

Exp Cell Res. 1996 Jan 10;222(1):38-47. doi: 10.1006/excr.1996.0005.

Abstract

Osteogenic protein-1 (OP-1, BMP-7), a bone morphogenetic protein in the transforming growth factor-beta superfamily, induces endochondral bone formation in vivo, but the mechanism of action of OP-1 in osteogenesis is not yet established. Three murine clonal cell lines in different stages of differentiation exhibit graded responses to recombinant human OP-1: the mouse embryonal carcinoma ATDC5 cell, with potential for chondroblastic differentiation; the osteoblast-like MC3T3-E1 cell derived from mouse calvaria; and the multipotent fibroblastic C3H10T1/2 cell derived from mouse embryo connective tissue. We show that OP-1 acts on early stage mesenchymal progenitor cells (ATDC5, C3H10T1/2) to induce chondroblastic differentiation, while OP-1 strongly enhances the osteoblastic phenotype of committed osteoblasts (MC3T3-E1), possibly explaining its induction of the endochondral ossification cascade in vivo. Markers of osteoblastic, chondroblastic, and adipocytic differentiation are compared. OP-1 is strongly mitogenic for ATDC5, showing dose-dependent (2.5-80 ng/ml) induction of Alcian blue staining, alkaline phosphatase activity, and mRNA expression for collagen types II and IX, and matrix Gla protein. MC3T3-E1 cells do not proliferate or stain with Alcian blue in response to OP-1, but express elevated levels of alkaline phosphatase and osteocalcin. While low-dose OP-1 treatment of C3H10T1/2 induces only adipocyte-like cells filled with lipid droplets, a high dose (500 ng/ml) causes the same cells to also exhibit chondrocytic properties. Thus, OP-1 can induce differentiation along elements of the endochondral ossification pathway according to the stage and potential of the target cell.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / cytology*
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins*
  • Carcinoma, Embryonal
  • Cartilage / cytology*
  • Cell Differentiation / drug effects
  • Clone Cells
  • Collagen / genetics
  • Fibroblasts / cytology*
  • Gene Expression / drug effects
  • Glycerolphosphate Dehydrogenase / metabolism
  • Glycosaminoglycans / analysis
  • Humans
  • Mice
  • Osteoblasts / cytology*
  • Osteocalcin / biosynthesis
  • Osteogenesis / drug effects
  • Proteins / pharmacology*
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta*

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Glycosaminoglycans
  • Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Osteocalcin
  • A73025
  • Collagen
  • Glycerolphosphate Dehydrogenase
  • Alkaline Phosphatase