Minocycline ameliorates osteoporosis induced by ovariectomy (OVX) and iron accumulation via iron chelation, bone metabolism regulation and inhibition of oxidative stress.

OBJECTIVE

To investigate the effect and mechanism of minocycline on iron accumulation-related postmenopausal osteoporosis.

METHODS

The present study established a rat model of ovariectomy (OVX), gave rats ferric ammonium citrate (FAC) and treated them with minocycline, then examined the severity of osteoporosis and iron metabolism in rats. To further explore the mechanism, osteoblasts were treated with FAC and minocycline, then their effects on cell viability, apoptosis, alkaline phosphatase (ALP) activity, bone metabolism proteins, iron metabolism proteins, and oxidative stress in osteoblasts were measured.

RESULTS

In the animal study, OVX significantly decreased the serum estradiol level. Both OVX and FAC significantly increased the serum ferritin and tibial iron level, which was significantly decreased by minocycline (P < 0.05). Minocycline significantly increased the ratio of BV/TV, Tb.Th and Tb.N (P < 0.05), and the levels of BALP, BGP and CTX, but decreased the levels of TRAP and ratio of RANKL/OPG (P < 0.05 compared to OVX+FAC group). In the cell study, minocycline significantly decreased the cellular iron accumulation and induced cell death and apoptosis (P < 0.05). Minocycline significantly increased the ALP activity, the expression of Collagen I, Osteocalcin and OPG (P < 0.05). Minocycline significantly decreased the expression of Ferritin and hepcidin, and increased the expression of FPN) (P < 0.05). It also significantly decreased the cellular MD) and protein carbonyl level and RO) intensity, but increased the levels of SO) and GP) (P < 0.05).

CONCLUSION

Minocycline ameliorated osteoporosis induced by OVX and iron accumulation. The mechanism may involve iron chelation, regulation of bone and iron metabolism, and inhibition of oxidative stress.