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Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone remodeling

Anne M Delany, Kurt David Hankenson

    Journal of Cell Communication and Signaling
    |October 29, 2009
    PubMed

    Insights

    Thrombospondin-2 and osteonectin/SPARC are key proteins regulating bone remodeling. Deficiencies in these proteins alter bone structure and cellular differentiation, impacting skeletal health.

    Area of Science:

    • Bone biology and skeletal remodeling.
    • Cellular and molecular mechanisms of bone formation.

    Background:

    • Matricellular proteins thrombospondin-2 (TSP2) and osteonectin/SPARC are highly expressed in bone cells.
    • Genetic deficiencies in TSP2 or SPARC lead to distinct skeletal phenotypes, particularly under altered bone remodeling conditions.
    • These proteins play crucial roles in regulating bone structure, function, and the remodeling process.

    Purpose of the Study:

    • To review the roles of TSP2 and SPARC in bone biology.
    • To summarize findings from in vitro and in vivo studies on TSP2 and SPARC.
    • To explore the impact of TSP2 and SPARC on osteoblastic differentiation and bone remodeling.

    Main Methods:

    • Analysis of phenotypes in TSP2-null and SPARC-null mouse models.
    • In vitro studies using marrow stromal cells (MSCs) from knockout mice.
    • Review of existing literature on TSP2 and SPARC in bone remodeling.

    Main Results:

    • TSP2-null mice exhibit higher cortical bone volume and resistance to ovariectomy-induced bone loss.
    • SPARC-null mice show decreased trabecular bone volume and impaired response to parathyroid hormone treatment.
    • In vitro, TSP2 deficiency increases MSC proliferation but delays matrix mineralization, while SPARC deficiency decreases osteoblastic differentiation and mineralization.

    Conclusions:

    • Both TSP2 and SPARC are positive regulators of osteoblastic differentiation and bone remodeling.
    • These matricellular proteins influence MSC fate, potentially through the Notch signaling pathway.
    • Understanding TSP2 and SPARC functions is critical for bone health and therapeutic strategies.

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