Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling.
Bone morphogenetic proteins (BMPs) function during various aspects of embryonic development including skeletogenesis. However, their biological functions after birth are less understood. To investigate the role of BMPs during bone remodeling, we generated a postnatal osteoblast-specific disruption of Bmpr1a that encodes the type IA receptor for BMPs in mice. Mutant mice were smaller than controls up to 6 months after birth. Irregular calcification and low bone mass were observed, but there were normal numbers of osteoblasts. The ability of the mutant osteoblasts to form mineralized nodules in culture was severely reduced. Interestingly, bone mass was increased in aged mutant mice due to reduced bone resorption evidenced by reduced bone turnover. The mutant mice lost more bone after ovariectomy likely resulting from decreased osteoblast function which could not overcome ovariectomy-induced bone resorption. In organ culture of bones from aged mice, ablation of the Bmpr1a gene by adenoviral Cre recombinase abolished the stimulatory effects of BMP4 on the expression of lysosomal enzymes essential for osteoclastic bone resorption. These results demonstrate essential and age-dependent roles for BMP signaling mediated by BMPRIA (a type IA receptor for BMP) in osteoblasts for bone remodeling.
Mishina
Yuji
Y
Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. mishina@niehs.nih.gov
Starbuck
Michael W
MW
Gentile
Michael A
MA
Fukuda
Tomokazu
T
Kasparcova
Viera
V
Seedor
J Gregory
JG
Hanks
Mark C
MC
Amling
Michael
M
Pinero
Gerald J
GJ
Harada
Shun-ichi
S
Behringer
Richard R
RR
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D001846:Bone Development; D052005:Bone Morphogenetic Protein Receptors, Type I; D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D005260:Female; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D010010:Osteoclasts / Q000378:metabolism; D010052:Ovariectomy; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D017978:Receptors, Growth Factor; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; C045073:Cre recombinase; D019426:Integrases; D000469:Alkaline Phosphatase