title: A new function of Nell-1 protein in repressing adipogenic differentiation.
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.
authors: Dental and Craniofacial Research Institute, University of California, Los Angeles, CA 90095, United States. aaronwjames1@gmail.com
authors: Aaron W
authors: AW
authors: James
authors: Angel
authors: A
authors: Pan
authors: Michael
authors: M
authors: Chiang
authors: Janette N
authors: JN
authors: Zara
authors: Xinli
authors: X
authors: Zhang
authors: Kang
authors: K
authors: Ting
authors: Chia
authors: C
authors: Soo
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D053823:Hedgehog Proteins; C104144:NELL1 protein, human; D009419:Nerve Tissue Proteins