β‑Ecdysterone promotes autophagy and inhibits apoptosis in osteoporotic rats

Abstract

Osteoporosis is an aging process of skeletal tissues with characteristics of reductions in bone mass and microarchitectural deterioration of bone tissue. The present study aimed to investigate the effects of glucocorticoid-induced osteoporosis on osteoblasts and to examine the roles of β-ecdysterone (β-Ecd) involved. In the present study, an in vivo model of osteoporosis was established through the subcutaneous implantation of prednisolone (PRED) into Sprague-Dawley rats, with or without a subcutaneous injection of β-Ecd (5 or 10 mg/kg body weight). Expression of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3I/II and apoptosis in lumbar vertebrae tissues was measured by immunofluorescence and TUNEL assays, respectively. Serum concentration of calcium and phosphorus, and the activity of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured by biochemical assay. Reverse transcription-quantitative polymerase chain reaction and western blotting was used for detect the expression of related genes and proteins. PRED treatment inhibited bone formation by decreasing bone mineral density, and suppressing the expression of Runt-related transcription factor 2 and bone morphogenetic protein 2, while enhancing the activity of alkaline phosphatase, upregulating the expression of receptor activator of nuclear factor-κB ligand, and increasing the serum content of calcium, phosphorus and tartrate-resistant acid phosphatase in rats. Additionally, PRED was revealed to inhibit autophagy through the downregulation of Beclin-1, autophagy protein 5 and microtubule-associated protein 1A/1B-light chain 3I/II expression, whereas it induced the apoptosis, through the activation of caspase-3 and the suppression of apoptosis regulator BCL2 expression. Notably, the PRED-induced alterations in bone formation, autophagy and apoptosis were revealed to be attenuated by β-Ecd administration. In conclusion, the findings of the present study suggested that β-Ecd may be a promising candidate for the development of therapeutic strategies for the treatment of osteoporosis, through the induction of autophagy and the inhibition of apoptosis in vivo.

β‐ecdysone promotes osteogenic differentiation of bone marrow mesenchymal stem cells

“…14 A recent study reported that βEcd possesses multiple pharmacological actions, including protection against β-amyloid-induced apoptosis. 15,16 Previously, βEcd was shown to increase the differentiation of mesenchymal progenitor cells towards osteoblasts in vitro, which is consistent with the observation of an increased osteoblast surface following in vivo βEcd treatment. 17 In the present study, hBMSCs were cultured with different concentrations of βEcd, and βEcd at 0, 25 and 50 μmol/l had no significant inhibitory effect on hBMSC viability.…”

Biological Factors, Metals, and Biomaterials Regulating Osteogenesis through Autophagy

“…The effects on cell differentiation and autophagy induced by dexamethasone were reversed by β-ecdysterone in a dose-dependent manner [69]. Similar results were obtained in vivo: in a murine model of osteoporois, β-ecdysterone was able to inhibit apoptosis through the induction of the autophagic process [70].…”

An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms

“…Ecdy can promote autophagy upon the onset of osteoporosis in rats (Tang et al, 2018). In addition, Ecdy protects from degeneration human nucleus pulposus cells, which form the inner core of the vertebral disc (Wen et al, 2019).…”

“…Tang and colleagues (Tang et al, 2018) has reported that ecdysterone promotes autophagy in osteoporotic rats. We have carried out staining in three ecdysterone-treated (0, 250, 500, and 750 μM, 48 h) breast cancer cell lines with LysoTracker, a fluorescent dye, reflecting the number of lysosomes which can be indicative of autophagy (Chikte et al, 2014).…”