Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

Abstract

Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling.

Salidroside Attenuates Adriamycin-Induced Focal Segmental Glomerulosclerosis by Inhibiting the Hypoxia-Inducible Factor-1α Expression Through Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

“…Based on these data, we guess that HIF-1α participates in the pathogenesis of FSGS through targeting inflammatory response and oxidative stress [15]. Recently, Li et al [16] have been reported the protective effect of SAL against bone loss via targeting HIF-1α, indicating the possible target of SAL in FSGS. Recently, the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signaling pathway has been shown to positively affect the translational as well as transcriptional initiation of the HIF-1α gene [17].…”

Qiliqiangxin attenuates hypoxia‐induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF‐1α‐dependent glycolysis

“…Previous studies showed that up‐regulated HIF‐1α activity was linked with reduced the apoptosis of various cell types including cardiomyocytes and human umbilical vein endothelial cells (HUVECs) 12, 13. On the contrary, suppressed HIF‐1α expression was related to reduction in angiogenesis and glycolysis, increase in ROS production and induction of apoptosis or death of endothelial cells, cancer cells and other cell types 14, 15, 16, 17, 18. Taken together, HIF‐1α is a key regulator of endothelium survival under hypoxic condition, and up‐regulation of HIF‐1α might be a key method of protecting endothelial cells from hypoxic injury.…”

Salidroside promotes human periodontal ligament cell proliferation and osteocalcin secretion via ERK1/2 and PI3K/Akt signaling pathways

“…Based on its pharmacological anti-hypoxic and pro-angiogenic effects, salidroside has anti-osteoporotic activity (1,11). Hypoxia or oxidative stress induced osteoblast apoptosis, decreased osteoblast activity, thus leading to a reduction of osteoblastic bone formation and bone loss, which was abrogated by salidroside treatment by enhancing angiogenesis and osteogenesis (1,11).…”

“…For instance, salidroside inhibits the development of lipopolysaccharide (LPS)-induced mastitis in mice by attenuating the LPS-triggered activation of NF-κB and MAPKs (6). Owing to its protective effects against oxidative stress, salidroside has exhibited activity against gastric ulcers (8), hydrogen peroxide-induced apoptosis (3), β-amyloid-induced cognitive deficits (9,10), bone loss (1,11) and various cancer types, including bladder cancer (12) and lung cancer (13), demonstrating the potential use of salidroside in inhibiting the development of these diseases.…”

“…Hypoxia or oxidative stress induced osteoblast apoptosis, decreased osteoblast activity, thus leading to a reduction of osteoblastic bone formation and bone loss, which was abrogated by salidroside treatment by enhancing angiogenesis and osteogenesis (1,11). Periodontitis is a chronic multifactorial inflammatory disease characterized by progressive destruction of the tooth supporting apparatus, enhanced cell apoptosis and tooth loss, or rather periodontal bone loss (14)(15)(16).…”