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dc.contributor.authorLiu, R
dc.contributor.authorGinn, SL
dc.contributor.authorLek, M
dc.contributor.authorNorth, KN
dc.contributor.authorAlexander, IE
dc.contributor.authorLittle, DG
dc.contributor.authorSchindeler, A
dc.date.accessioned2021-02-05T01:16:29Z
dc.date.available2021-02-05T01:16:29Z
dc.date.issued2009-05-15
dc.identifierpii: 1471-2474-10-51
dc.identifier.citationLiu, R., Ginn, S. L., Lek, M., North, K. N., Alexander, I. E., Little, D. G. & Schindeler, A. (2009). Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a. BMC MUSCULOSKELETAL DISORDERS, 10 (1), https://doi.org/10.1186/1471-2474-10-51.
dc.identifier.issn1471-2474
dc.identifier.urihttp://hdl.handle.net/11343/260332
dc.description.abstractBACKGROUND: Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression. METHODS: We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD) were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes (alkaline phosphatase, osteocalcin and bone morphogenetic protein receptor-1A) as measured by quantitative PCR. RESULTS: BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated Bmpr-1a expression. Chronic BMP-2 treatment resulted in peak Bmpr-1a expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of Bmpr-1a that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine BMPR-1A/Bmpr-1a. Forced myogenic gene expression in fibroblasts was associated with a significant increase in Bmpr-1a expression and a synergistic increase in the osteogenic response to BMP-2. CONCLUSION: These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2.
dc.languageEnglish
dc.publisherBMC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMyoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a
dc.typeJournal Article
dc.identifier.doi10.1186/1471-2474-10-51
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleBMC Musculoskeletal Disorders
melbourne.source.volume10
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1051659
melbourne.contributor.authorNorth, Kathryn
dc.identifier.eissn1471-2474
melbourne.accessrightsOpen Access


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