Sodium hydrosulfide alleviates dexamethasone‑induced cell senescence and dysfunction through targeting the miR‑22/sirt1 pathway in osteoblastic MC3T3‑E1 cells

Abstract

Glucocorticoid-induced osteoporosis is characterized by osteoblastic cell and microarchitecture dysfunction, as well as a loss of bone mass. Cell senescence contributes to the pathological process of osteoporosis and sodium hydrosulfide (NaHS) regulates the potent protective effects through delaying cell senescence. The aim of the present study was to investigate whether senescence could contribute to dexamethasone (Dex)-induced osteoblast impairment and to examine the effect of NaHS on Dex-induced cell senescence and damage. It was found that the levels of the senescence-associated markers, p53 and p21, were markedly increased in osteoblasts exposed to Dex. A p53 inhibitor reversed Dex-induced osteoblast injury, a process that was mitigated by NaHS administration through alleviating osteoblastic cell senescence. MicroRNA (miR)-22 blocked the impact of NaHS on Dex-induced osteoblast damage and senescence through targeting the regulation of Sirtuin 1 (sirt1) expression, as shown by the decreased cell viability and alkaline phosphatase activity, as well as an increased expression of p53 and p21. It was revealed that the sirt1 gene was the target of miR-22 in osteoblastic MC3T3-E1 cells through combining the results of dual luciferase reporter assays and reverse transcription-quantitative PCR, as well as western blot analyses. Silencing of sirt1 abolished the protective effect of NaHS against Dex-associated osteoblast senescence and injury. Taken together, the present study showed that NaHS prevents Dex-induced cell senescence and damage through targeting the miR-22/sirt1 pathway in osteoblastic MC3T3-E1 cells.

Metformin attenuates H2O2‑induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

“…MC3T3-E1 cells were cultured in α-Minimal Essential Medium (HyClone; Cytiva) supplemented with 10% fetal bovine serum (HyClone; Cytiva), 100 U/ml streptomycin sulfate and 100 mg/ml penicillin. Cells were grown in a humidified incubator with 5% CO 2 at 37˚C ( 18 ). H 2 O 2 was added to the medium to induce an oxidative damage model at a concentration gradient of 0.1, 0.2 and 0.3 mM.…”

SIRT1 targeted by miR‐211‐5p regulated proliferation and apoptosis of Dex‐treated growth plate chondrocytes via mediating SOX2

“…14,15 SIRT1 downregulation is also reported to be involved in the regulation of dexamethasone-induced osteoblastic dysfunction, chondrocyte matrix degeneration and osteoporosis. [16][17][18] Nevertheless, the regulatory mechanism of SIRT1 in Dex-induced growth retardation remains unclear.…”

“…Importantly, previous studies have suggested that SIRT1 promoted growth plate chondrogenesis and longitudinal bone growth 14,15 . SIRT1 downregulation is also reported to be involved in the regulation of dexamethasone‐induced osteoblastic dysfunction, chondrocyte matrix degeneration and osteoporosis 16–18 . Nevertheless, the regulatory mechanism of SIRT1 in Dex‐induced growth retardation remains unclear.…”

miR‑27b attenuates dexamethasone‑inhibited proliferation and osteoblastic differentiation in MC3T3‑E1 cells by targeting PPARγ2

“…An increasing number of studies have suggested that osteoblast dysfunction disrupts the balance between bone resorption and bone formation by inhibiting osteoblast differentiation and proliferation, and enhancing osteoblast apoptosis in glucocorticoid-induced osteoporosis ( 26 , 27 ). Exposure to dexamethasone (DEX) induced the apoptosis of osteoblasts and inhibited MC3T3-E1 cell proliferation ( 28 ).…”