Effects of BMP-2 and vitamin D3 on the osteogenic differentiation of adipose stem cells |
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| Authors: | Song Insun Kim Byung-Soo Kim Chang-Sung Im Gun-Il |
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| Affiliation: | aDental and Craniofacial Research Institute, University of California, Los Angeles, CA 90095, United States;bSection of Orthodontics School of Dentistry, University of California, Los Angeles, CA 90095, United States;cUCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, CA 90095, United States |
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| Abstract: | A theoretical inverse relationship has long been postulated for osteogenic and adipogenic differentiation (bone versus adipose tissue differentiation). This inverse relationship in theory at least partially underlies the clinical entity of osteoporosis, in which marrow mesenchymal stem cells (MSCs) have a predilection for adipose differentiation that increases with age. In the present study, we assayed the potential anti-adipogenic effects of Nell-1 protein (an osteoinductive molecule). Using 3T3-L1 (a human preadipocyte cell line) cells and human adipose-derived stromal cells (ASCs), we observed that adenoviral delivered (Ad)-Nell-1 or recombinant NELL-1 protein significantly reduced adipose differentiation across all markers examined (Oil red O staining, adipogenic gene expression [Pparg, Lpl, Ap2]). In a prospective fashion, Hedgehog signaling was assayed as potentially downstream of Nell-1 signaling in regulating osteogenic over adipogenic differentiation. In comparison to Ad-LacZ control, Ad-Nell-1 increased expression of hedgehog signaling markers (Ihh, Gli1, Ptc1). These studies suggest that Nell-1 is a potent anti-adipogenic agent. Moreover, Nell-1 signaling may inhibit adipogenic differentiation via a Hedgehog dependent mechanism. |
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| Keywords: | Nell-1 Osteogenic differentiation Adipogenic differentiation Sonic Hedgehog Indian Hedgehog |
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