Dental and Craniofacial Research Institute, University of California, Los Angeles, CA 90095, United States.
Biochem Biophys Res Commun. 2011 Jul 22;411(1):126-31. doi: 10.1016/j.bbrc.2011.06.111. Epub 2011 Jun 23.
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.
成骨细胞与成脂细胞分化（骨与脂肪组织分化）之间一直存在理论上的反向关系。这种反向关系至少部分地构成了骨质疏松症的临床实体，其中骨髓间充质干细胞（MSCs）倾向于脂肪分化，这种分化随年龄的增长而增加。在本研究中，我们检测了 Nell-1 蛋白（一种成骨诱导分子）的潜在抗脂肪生成作用。使用 3T3-L1（一种人前脂肪细胞系）细胞和人脂肪来源的基质细胞（ASCs），我们观察到，腺病毒传递的（Ad）-Nell-1 或重组 NELL-1 蛋白显著降低了所有检测到的标记物的脂肪分化（油红 O 染色、脂肪生成基因表达[Pparg、Lpl、Ap2]）。前瞻性地检测 Hedgehog 信号转导作为 Nell-1 信号转导在调节成骨细胞与脂肪细胞分化中的潜在下游信号转导。与 Ad-LacZ 对照相比，Ad-Nell-1 增加了 Hedgehog 信号转导标记物（Ihh、Gli1、Ptc1）的表达。这些研究表明，Nell-1 是一种有效的抗脂肪生成剂。此外，Nell-1 信号转导可能通过 Hedgehog 依赖的机制抑制脂肪生成分化。
