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Mast4 determines the cell fate of MSCs for bone and cartilage development

 Pyunggang Kim  ;  Jinah Park  ;  Dong-Joon Lee  ;  Seiya Mizuno  ;  Masahiro Shinohara  ;  Chang Pyo Hong  ;  Yealeen Jeong  ;  Rebecca Yun  ;  Hyeyeon Park  ;  Sujin Park  ;  Kyung-Min Yang  ;  Min-Jung Lee  ;  Seung Pil Jang  ;  Hyun-Yi Kim  ;  Seung-Jun Lee  ;  Sun U Song  ;  Kyung-Soon Park  ;  Mikako Tanaka  ;  Hayato Ohshima  ;  Jin Won Cho  ;  Fumihiro Sugiyama  ;  Satoru Takahashi  ;  Han-Sung Jung  ;  Seong-Jin Kim 
 NATURE COMMUNICATIONS, Vol.13(1) : 3960, 2022-07 
Journal Title
Issue Date
Animals ; Cartilage / metabolism ; Cell Differentiation / genetics ; Cells, Cultured ; Chondrogenesis ; Glycogen Synthase Kinase 3 beta / metabolism ; Mesenchymal Stem Cells* / metabolism ; Mice ; Microtubule-Associated Proteins / metabolism* ; Osteogenesis* / genetics ; Protein Serine-Threonine Kinases / metabolism* ; Serine / metabolism ; Wnt Signaling Pathway
Mesenchymal stromal cells (MSCs) differentiation into different lineages is precisely controlled by signaling pathways. Given that protein kinases play a crucial role in signal transduction, here we show that Microtubule Associated Serine/Threonine Kinase Family Member 4 (Mast4) serves as an important mediator of TGF-β and Wnt signal transduction in regulating chondro-osteogenic differentiation of MSCs. Suppression of Mast4 by TGF-β1 led to increased Sox9 stability by blocking Mast4-induced Sox9 serine 494 phosphorylation and subsequent proteasomal degradation, ultimately enhancing chondrogenesis of MSCs. On the other hand, Mast4 protein, which stability was enhanced by Wnt-mediated inhibition of GSK-3β and subsequent Smurf1 recruitment, promoted β-catenin nuclear localization and Runx2 activity, increasing osteogenesis of MSCs. Consistently, Mast4-/- mice demonstrated excessive cartilage synthesis, while exhibiting osteoporotic phenotype. Interestingly, Mast4 depletion in MSCs facilitated cartilage formation and regeneration in vivo. Altogether, our findings uncover essential roles of Mast4 in determining the fate of MSC development into cartilage or bone.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Hyun-Yi(김현이)
Lee, Dong Joon(이동준) ORCID logo https://orcid.org/0000-0001-6532-9729
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
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