Abstract
Postmenopausal osteoporosis is a common condition characterized by the increase and activation of osteoclasts. The present study aimed to investigate the effects of extracellular signal-regulated kinase (ERK) 5 (ERK-5) on postmenopausal osteoporosis by regulating the biological behaviors of osteoblasts. Sprague–Dawley (SD) rats were ovariectomized to develop an osteoporosis model. A lentivirus packaging system was employed to generate lentiviruses capable of up- or down-regulating the expression of ERK-5 in ovariectomized rats. The femoral biomechanical properties, bone mineral density (BMD), contents of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) and bone turnover markers in rats, as well as viability, cycle and apoptosis of osteoblasts and ALP activity in osteoblasts were measured in the ovariectomized rats so as to explore the functional significance of ERK-5 in postmenopausal osteoporosis. The femoral mechanical strength of ovariectomized rats was enhanced by overexpression of ERK-5. Meanwhile femoral BMD, and bone metabolism were increased, and bone turnover normalized in the ovariectomized rats when ERK-5 was overexpressed. Lentivirus-mediated ERK-5 overexpression in osteoblasts was observed to inhibit osteoblast apoptosis, and promote viability, accompanied with increased ALP activity. Taken together, ERK-5 could decelerate osteoblast apoptosis and improve postmenopausal osteoporosis by increasing osteoblast viability. Thus, our study provides further understanding on a promising therapeutic target for postmenopausal osteoporosis.
Highlights
Osteoporosis is a chronic progressive disease characterized by the deterioration of bone microstructure, low bone mass, bone fragility and increasing risk of fracture [1,2]
The rats in our study were ovariectomized to stimulate postmenopausal osteoporosis to identify the role of extracellular signal-regulated kinase 5 (ERK-5) in the proliferation and apoptosis of osteoblasts
The study concluded that extracellular signal-regulated kinase (ERK)-5 could improve the properties of femoral tissues, which inhibits the apoptosis and promotes proliferation of osteoblasts, improving postmenopausal osteoporosis
Summary
Osteoporosis is a chronic progressive disease characterized by the deterioration of bone microstructure, low bone mass, bone fragility and increasing risk of fracture [1,2]. Numerous patients suffering from osteoporosis-caused fractures often fail to be correctly diagnosed which results in failure to receive valid therapies admitted by Food and Drug Administration [3]. The disability and mortality instigated by osteoporosis greatly affect the life quality of the aging population, in patients over 65 even though the lifestyle changes could lower the osteoporosis risks [7]. The development of novel treatment methods as well as improvement to existing osteoporosis treatment methods has been largely limited because of the difficulties encountered in establishing drugs capable of influencing the progression of the disease [2]. Due to the limitations of License 4.0 (CC BY)
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