Abstract
Mesenchymal stem cell (MSC)-mediated tissue engineering represents a promising strategy to address adipose tissue defects. MSCs derived from Wharton’s jelly of the umbilical cord (WJCMSCs) may serve as an ideal source for adipose tissue engineering due to their abundance, safety profile, and accessibility. How to activate the directed differentiation potentials of WJCMSCs is the core point for their clinical applications. A thorough investigation of mechanisms involved in WJCMSC adipogenic differentiation is necessary to support their application in adipose tissue engineering and address shortcomings. Previous study showed, compared with periodontal ligament stem cells (PDLSCs), WJCMSCs had a weakened adipogenic differentiation potentials and lower expression of insulin-like growth factor binding protein 2 (IGFBP2). IGFBP2 may be involved in the adipogenesis of MSCs. Generally, IGFBP2 is involved in regulating biological activity of insulin-like growth factors, however, its functions in human MSCs are unclear. Here, we found IGFBP2 expression was upregulated upon adipogenic induction, and that IGFBP2 enhanced adipogenic differentiation of WJCMSCs and BMSCs. Moreover, IGFBP2 increased phosphorylation of c-Jun N-terminal kinase (p-JNK) and p-Akt, and activated JNK or Akt signaling significantly promoted adipogenic differentiation of MSCs. Furthermore, inhibitor-mediated blockage of either JNK or Akt signaling dramatically reduced IGFBP2-mediated adipogenic differentiation. And the JNK inhibitor, SP600125 markedly blocked IGFBP2-mediated Akt activation. Moreover, IGFBP2 was negatively regulated by BCOR, which inhibited adipogenic differentiation of WJCMSCs. Overall, our results reveal a new function of IGFBP2, providing a novel insight into the mechanism of adipogenic differentiation and identifying a potential target mediator for improving adipose tissue engineering based on WJCMSCs.
Highlights
Adipose tissue plays an essential role in the maintenance of organ contours, energy storage, metabolic balance, and immune regulation through exocrine hormones and fat cell factors
We consistently found lower insulin-like growth factor binding protein 2 (IGFBP2) expression in WJCMSCs (0.00388±0.00033) than that in periodontal ligament stem cells (PDLSCs) (1±0.0347), bone marrow mesenchymal stem cells (BMSCs) (0.1225±0.011), and adipose-derived stem cells (ASCs) (0.364 ±0.023) (Fig 1A)
After normalizing the data with total protein, these results suggested that WJCMSC-Flag-IGFBP2 cells had stronger adipogenic differentiation potential (Fig 2D)
Summary
Adipose tissue plays an essential role in the maintenance of organ contours, energy storage, metabolic balance, and immune regulation through exocrine hormones and fat cell factors. MSCs have been isolated from various tissues, including bone marrow, adipose tissue, vascular tissue, dental tissue, craniofacial tissue, and umbilical cord [1,2,3,4,5,6,7]. With their convenient isolation, low immunogenicity, and ability to transdifferentiate, MSCs are considered a promising therapeutic approach for tissue regeneration [1,4,5,8,9]. A crucial issue for WJCMSCs-mediated adipose tissue regeneration is how to activate adipogenic differentiation and enhance regenerative ability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
