A new function of Nell-1 protein in repressing adipogenic differentiation

Aaron W. James, Angel Pan, Michael Chiang, Janette N. Zara, Xinli Zhang, Kang Ting, Chia Soo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)126-131
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume411
Issue number1
DOIs
StatePublished - Jul 22 2011
Externally publishedYes

Keywords

  • Adipogenic differentiation
  • Indian Hedgehog
  • Nell-1
  • Osteogenic differentiation
  • Sonic Hedgehog

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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