Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin.
Bone morphogenetic proteins (BMPs) have been heretofore implicated in the induction of osteoblast differentiation from uncommitted progenitors during embryonic skeletogenesis and fracture healing. We have tested the hypothesis that BMPs are also involved in the osteoblastogenesis that takes place in the bone marrow in postnatal life. To do this, we took advantage of the properties of noggin, a recently discovered protein that binds BMP-2 and -4 and blocks their action. Addition of human recombinant noggin to bone marrow cell cultures from normal adult mice inhibited both osteoblast and osteoclast formation; these effects were reversed by exogenous BMP-2. Consistent with these findings, BMP-2 and -4 and BMP-2/4 receptor transcripts and proteins were detected in these primary cultures, in a bone marrow-derived stromal/osteoblastic cell line, as well as in murine adult whole bone; noggin expression was also documented in all these preparations. Moreover, addition of antinoggin antibody caused an increase in osteoblast progenitor formation. These findings suggest that BMP-2 and -4 are expressed in the bone marrow in postnatal life and serve to maintain the continuous supply of osteoblasts and osteoclasts; and that, in fact, BMP-2/4-induced commitment to the osteoblastic lineage is a prerequisite for osteoclast development. Hence, BMPs, perhaps in balance with noggin and possibly other antagonists, may provide the tonic baseline control of the rate of bone remodeling on which other inputs (e.g., hormonal, biomechanical, etc.) operate.
Abe
E
E
Division of Endocrinology and Metabolism and the UAMS Center for Osteoporosis and Metabolic Bone Diseases, Little Rock, Arkansas, USA.
Yamamoto
M
M
Taguchi
Y
Y
Lecka-Czernik
B
B
O'Brien
C A
CA
Economides
A N
AN
Stahl
N
N
Jilka
R L
RL
Manolagas
S C
SC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011506:Proteins / Q000494:pharmacology*; D017978:Receptors, Growth Factor / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C499469:recombinant human bone morphogenetic protein-2; C498218:BMPR2 protein, human; C498219:Bmpr2 protein, mouse