Stimulatory effects of cartilage-derived morphogenetic proteins 1 and 2 on osteogenic differentiation of bone marrow stromal cells.
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.
Gruber
R
R
Department of Rheumatology, Clinic of Internal Medicine III, Austria.
Mayer
C
C
Schulz
W
W
Graninger
W
W
Peterlik
M
M
Watzek
G
G
Luyten
F P
FP
Erlacher
L
L
D029404:Activin Receptors; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000378:metabolism*; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D011416:Complement Factor D; D016895:Culture Media, Serum-Free / Q000378:metabolism; D017931:DNA Primers / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015675:Osteocalcin / Q000378:metabolism; D010641:Phenotype; D011347:Procollagen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D013696:Temperature; D016212:Transforming Growth Factor beta
C525816:BMP6 protein, human; C525819:BMP7 protein, human; C525817:Bmp6 protein, mouse; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; D017931:DNA Primers; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D011347:Procollagen; D016212:Transforming Growth Factor beta; C090394:cartilage-derived-morphogenetic protein-2; D015675:Osteocalcin; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; D000469:Alkaline Phosphatase; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse