Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling

Yuji Mishina, Michael W. Starbuck, Michael A. Gentile, Tomokazu Fukuda, Viera Kasparcova, J. Gregory Seedor, Mark C. Hanks, Michael Amling, Gerald J. Pinero, Shun Ichi Harada, Richard R. Behringer

    Research output: Contribution to journalArticlepeer-review

    164 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)27560-27566
    Number of pages7
    JournalJournal of Biological Chemistry
    Issue number26
    Publication statusPublished - 2004 Jun 25

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology


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