Tissue Eng Regen Med.  2020 Apr;17(2):193-202. 10.1007/s13770-019-00237-4.

Primary Cilia Mediate Wnt5a/β-catenin Signaling to Regulate Adipogenic Differentiation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Following Calcium Induction

• Bae YK
• Kim GH
• Kwon JH
• Kim M
• Choi SJ
• Oh W
• Um S
• Jin HJ

• KMID: 2509397
• DOI: http://doi.org/10.1007/s13770-019-00237-4

Abstract

Background
Regeneration of soft tissue defects is essential for adipose tissue pathologies and disease, trauma, or injury-induced damage. Here, we show that umbilical cord blood-derived mesenchymal stem cells could potentially be tailored and used for the reconstruction of specific damaged sites. Adipogenesis can be exploited in soft tissue reconstruction. Also, primary cilia play a role in the control of adipogenesis.
Methods
The adipogenic differentiation capacity of mesenchymal stem cells (MSCs) was shown to influence ciliogenesis. MSCs transfected with intraflagellar transport 88 (IFT88) small interfering RNA (siRNA), which blocks the assembly and maintenance of cilia, were examined to confirm the relationship between adipogenesis and ciliogenesis. Also, 1,2-Bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), calcium chelator, inhibited the ciliogenesis of MSCs in adipogenic differentiation.
Results
IFT88-knockdown led to decreased cilia formation and limitation of cilia elongation in adipogenesis. Additionally, intracellular calcium triggered cilia formation in MSCs adipogenesis. Interestingly, intracellular calcium cannot overcome the inhibition of adipogenesis caused by low numbers of cilia in MSCs.
Conclusion
Our data suggested that ciliogenesis was negatively regulated by Wnt5a/β-catenin signaling during adipogenesis. Thus, we suggest that calcium induction triggers adipogenesis and ciliogenesis.

Keyword

Adipogenesis; Mesenchymal stem cell; Cilia; Calcium; Wnt