摘要
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.
基金
This research was supported by the Division of Intramural Research,National Institute of Dental and Craniofacial Research,a part of the Intramural Research Program of the National Institutes of Health,Department of Health and Human Services.Open Access funding provided by the National Institutes of Health(NIH).
