Glucosylceramide synthase regulates adipo-osteogenic differentiation through synergistic activation of PPARγ with GlcCer
Cited 0 times inCited 0 times in
- Glucosylceramide synthase regulates adipo-osteogenic differentiation through synergistic activation of PPARγ with GlcCer
- Jang, Hyun-Jun; Lim, Seyoung; Kim, Jung-Min; Yoon, Sora; Lee, Chae Young; Hwang, Hyeon-Jeong; Shim, Jeong Woo; Shin, Kyeong Jin; Kim, Hye Yun; Park, Kwang Il; Nam, Dougu; Lee, Ja Yil; Yea, Kyungmo; Hirabayashi, Yoshio; Lee, Yu Jin; Chae, Young Chan; Suh, Pann-Ghill; Choi, Jang Hyun
- Issue Date
- Federation of American Societies for Experimental Biology
- FASEB JOURNAL, v.34, no.1, pp.1270 - 1287
- Dysregulation of the adipo‐osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and osteoporosis. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation; however, the detailed underlying mechanisms are largely unknown. Here, we demonstrate that glucosylceramide (GlcCer) and its synthase, glucosylceramide synthase (GCS), are key determinants of MSC differentiation into adipocytes or osteoblasts. GCS expression was increased during adipogenesis and decreased during osteogenesis. Targeting GCS using RNA interference or a chemical inhibitor enhanced osteogenesis and inhibited adipogenesis by controlling the transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ). Treatment with GlcCer sufficiently rescued adipogenesis and inhibited osteogenesis in GCS knockdown MSCs. Mechanistically, GlcCer interacted directly with PPARγ through A/B domain and synergistically enhanced rosiglitazone‐induced PPARγ activation without changing PPARγ expression, thereby treatment with exogenous GlcCer increased adipogenesis and inhibited osteogenesis. Animal studies demonstrated that inhibiting GCS reduced adipocyte formation in white adipose tissues under normal chow diet and high‐fat diet feeding and accelerated bone repair in a calvarial defect model. Taken together, our findings identify a novel lipid metabolic regulator for the control of MSC differentiation and may have important therapeutic implications.
- Appears in Collections:
- SLS_Journal Papers
- Files in This Item:
- There are no files associated with this item.
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.