Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells

Cytokine. 2000 Nov;12(11):1630-8. doi: 10.1006/cyto.2000.0760.

Abstract

Cartilage-derived morphogenetic proteins 1 and 2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family which play an important role in embryonic skeletal development. Throughout adult life, bone marrow-derived precursor cells maintain their ability to differentiate into osteoblasts in response to local growth factors. This study examines the osteogenic potential of CDMP-1, CDMP-2, BMP-6 and osteogenic protein 1 (OP-1) in bone marrow stromal cells (BMSC) and investigates the endogenous expression of CDMPs/BMPs and their respective activin receptor-like kinase (ALK) receptors. A 4-day exposure of BMSC to CDMP-1, CDMP-2, BMP-6, and OP-1 under serum-free conditions stimulated the progression of the osteogenic lineage in a dose-dependent manner as evaluated by alkaline phosphatase activity and osteocalcin synthesis. In contrast to the BMPs, CDMP-1 and especially CDMP-2 were significantly less osteogenic, as confirmed by Northern blot analysis. Moreover, BMSC were shown to express endogenously CDMP-2, BMP-2 to -6 and ALK-1, -2, -3, -5 and -6. Phenotypic characterization of BMSC by RT-PCR showed transcripts of the fat marker adipsin and the prechondrocytic marker procollagen type IIA; however, we were unable to detect the mature cartilage markers, procollagen type IIB and aggrecan, even after growth factor treatment. Our data indicate that CDMP-1, CDMP-2, BMP-6 and OP-1 enhance the osteogenic phenotype in BMSC, with CDMPs being clearly less osteogenic than BMPs. The endogenous expression of a variety of CDMPs/BMPs and their respective ALK receptors, suggests a possible involvement of these growth factors in the osteogenic differentiation of bone marrow progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors
  • Alkaline Phosphatase / metabolism
  • Animals
  • Blotting, Northern
  • Bone Marrow Cells / metabolism*
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / metabolism
  • Bone and Bones / cytology*
  • Bone and Bones / metabolism*
  • Cell Differentiation
  • Cell Division / drug effects
  • Complement Factor D
  • Culture Media, Serum-Free / metabolism
  • DNA Primers / metabolism
  • Dose-Response Relationship, Drug
  • Growth Differentiation Factor 5
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • Humans
  • Mice
  • Osteocalcin / metabolism
  • Phenotype
  • Procollagen / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / metabolism
  • Stromal Cells / metabolism*
  • Temperature
  • Transforming Growth Factor beta*

Substances

  • BMP6 protein, human
  • BMP7 protein, human
  • Bmp6 protein, mouse
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Culture Media, Serum-Free
  • DNA Primers
  • Growth Differentiation Factor 5
  • Growth Substances
  • Procollagen
  • Transforming Growth Factor beta
  • cartilage-derived-morphogenetic protein-2
  • Osteocalcin
  • Protein-Serine-Threonine Kinases
  • Activin Receptors
  • Alkaline Phosphatase
  • Serine Endopeptidases
  • CFD protein, human
  • Complement Factor D
  • complement factor D, mouse