| 1 | Secreted frizzled related-protein 2(Sfrp2)deficiency decreases adult skeletal stem cell function in mice显示文摘In a previous transcriptomic study of human bone marrow stromal cells(BMSCs,also known as bone marrow-derived^mesenchymal stem cells#,)/SFRP2 was highly over-represented in a subset of multipotent BMSCs(skeletal stem cells,SSCs),which recreate a bone/marrow organ in an in vivo ectopic bone formation assay.SFRPs modulate WNT signaling,which is essential to maintain skeletal homeostasis,but the specific role of SFRP2 in BMSCs/SSCs is unclear.Here,we evaluated Sfrp2 deficiency on BMSC/SSC function in models of skeletal organogenesis and regeneration.The skeleton of Sfrp2-def\c\ent(KO)mice is overtly normal;but their BMSCs/SSCs exhibit reduced colony-forming efficiency,reflecting low SSC self-renewal/abundancy.Sfrp2 KO BMSCs/SSCs formed less trabecular bone than those from WT littermates in the ectopic bone formation assay.Moreover,regeneration of a cortical drilled hole defect was dramatically impaired in Sfrp2 KO mice.Sfrp2-deficient BMSCs/SSCs exhibited poor in vitro osteogenic differentiation as measured by Runx2 and Osterix expression and calcium accumulation.Interestingly,activation of the Wnt co-receptor;Lrp6,and expression of Wnt target genes,Axin2,C-myc and Cyclin Dl,were reduced in Sfrp2-deficient BMSCs/SSCs.Addition of recombinant Sfrp2 restored most of these activities,suggesting that Sfrp2 acts as a Wnt agonist.We demonstrate that Sfrp2 plays a role in self-renewal of SSCs and in the recruitment and differentiation of adult SSCs during bone healing.SFRP2 is also a useful marker of BMSC/SSC multipotency,and a factor to potentially improve the quality of ex vivo expanded BMSC/SSC products. | Luis Fernandez de Castro Brian丄Sworder Byron Mui Kathryn Futrega Agnes Berendsen Matthew D.Phillips Nathan J.Burbach Natasha Cherman Sergei Kuznetsov Yankel Gabet Kenn Holmbeck Pamela G.Robey | 2021 | Bone Research2021，9，4： | 0 |
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