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

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.

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.

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.

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.