Effect of Mesenchymal Stem Cells Overexpressing BMP-9 Primed with Hypoxia on BMP Targets, Osteoblast Differentiation and Bone Repair.

Autor:	Paz JERM; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Adolpho LF; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Ramos JIR; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Bighetti-Trevisan RL; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Calixto RD; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Oliveira FS; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Almeida ALG; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Beloti MM; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil., Rosa AL; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café, s/n, Ribeirão Preto 14040-904, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Biology [Biology (Basel)] 2023 Aug 19; Vol. 12 (8). Date of Electronic Publication: 2023 Aug 19.
DOI:	10.3390/biology12081147
Abstrakt:	Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs +BMP-9 ) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs +BMP-9 and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated. Hypoxia was induced with cobalt chloride (CoCl 2 ) in MSCs +BMP-9 , and the expression of BMP components and targets was evaluated. The paracrine effects of hypoxia-primed MSCs +BMP-9 on cell viability and migration and osteoblast differentiation were evaluated using conditioned medium. The bone formation induced by hypoxia-primed MSCs +BMP-9 directly injected into rat calvarial defects was also evaluated. The results demonstrated that hypoxia regulated BMP components and targets without affecting BMP-9 amount and that the conditioned medium generated under hypoxia favored cell migration and osteoblast differentiation. Hypoxia-primed MSCs +BMP-9 did not increase bone repair compared with control MSCs +BMP-9 . Thus, despite the lack of effect of hypoxia on bone formation, the enhancement of cell migration and osteoblast differentiation opens windows for further investigations on approaches to modulate the BMP-9-HIF-1α circuit in the context of cell-based therapies to induce bone regeneration.
Databáze:	MEDLINE
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