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Title

Effect of human adipose-derived mesenchymal stem cells preconditioned with cobalt chloride for hypoxia induction on ovariectomy-induced osteoporosis

Pages

  679-689

Abstract

 2Introduction: Osteoporosis (OP) is a chronic metabolic disease. Cobalt (II) chloride (CoCl2) induces favorable effects on hAD-MSCs (human Adipose-Derived Mesenchymal Stem Cells) function. This study aimed to assess the effects of CoCl2-preconditioned hAD-MSCs injection for Hypoxia induction in female rats with ovariectomy-induced OP. Materials and Methods: 24 adult female rats were subjected to bilateral ovariectomy. After 3.5 months, the OP progression was evaluated using CT scanning procedures with densitometric evaluation. Then, the animals were divided into 3 groups: sham (control), normoxia, and Hypoxia groups receiving PBS (Phosphate Buffered Saline), hAD-MSCs, and 100 µM CoCl2-exposed hAD-MSCs for 48 h, respectively, via the tail vein. After 2 months, to investigate the Hypoxia-inducing factor-1α (HIF-1α) by western blot analysis and to assess growth factors Insulin-like Growth Factor (IGF1) and Transforming Growth Factor Beta (TGFβ) and pro-inflammatory cytokines Tumor Necrosis Factor Alpha (TNFα) and Interleukin-1beta (IL-1β) using the ELISA (Enzyme-Linked Immunosorbent Assay) method, sampling of right and left tibia bone tissue markers was respectively done. Results: In the group receiving 100 µM CoCl2-pretreated hAD-MSCs for 48 h, compared to the groups receiving normoxia cells and PBS, an increase in the expression of HIF-1α (P> 0.01 and P> 0.001), IGF-I (P> 0.01 and P>0.001), and TGF-β (P> 0.05 and P> 0.01), and a decrease in the expression of TNF-α and IL-1β (P> 0.001 and P>0.01) were significantly observed in right and left tibia bone, respectively. Conclusion: CoCl2 led to increased efficiency and effectiveness of CoCl2-pretreated hAD-MSCs in reducing the expression of pro-inflammatory cytokines and increasing growth factors through increasing the expression of HIF-1α.

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