Abstract
Osteoporosis, which is a systemic skeletal disease characterized by low bone mineral density and microarchitectural deterioration of bone quality, is a global and increasing public health problem. Recent studies have suggested that Tenuigenin (TEN), a class of native compounds with numerous biological activities such as anti-resorptive properties, exerts protective effects against postmenopausal bone loss. The present study aims to investigate the osteogenic effects of TEN on bone mesenchymal stem cells (BMSCs) in vitro and in vivo. Alkaline phosphatase (ALP) activity/staining, Alizarin red staining and the expression of osteogenic markers, including runt-related transcription factor 2, osterix, osteocalcin, collagen Iα1, β-catenin and glycogen synthase kinase-3β were investigated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of TEN. An ovariectomized (OVX) mouse model was used to investigate the effect of TEN treatment for 3 months in vivo. We found that ALP activity, mineralized nodules and the expression of osteogenic markers were increased and WNT/β-catenin signaling was enhanced in vitro and in vivo. Bone parameters, including trabecular thickness, trabecular number and bone mineral density were higher in the OVX+TEN group than in control OVX mice. Our results suggest the therapeutic potential of TEN for the treatment of patients with postmenopausal osteoporosis.
Highlights
Osteoporosis (OP) is a common and systemic skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone quality that reduces bone strength, with a consequent increased risk of fragile fractures
To examine the effects of TEN on osteogenic differentiation, bone mesenchymal stem cells (BMSCs) were treated with TEN (4, 8 and 16 μg/ml) in osteogenic medium for 14 days
Alkaline phosphatase (ALP) activity/staining and Alizarin red staining were measured and the expression of the osteogenic markers Runx2, OSX, OCN and collagen Iα1 (Col Iα1) was determined by Quantitative reverse transcription Polymerase chain reaction (PCR) (qRT-PCR), Western blot (WB), or immunostaining
Summary
Osteoporosis (OP) is a common and systemic skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone quality that reduces bone strength, with a consequent increased risk of fragile fractures (van den Bergh et al 2012). Osteoporosis increases the frequency of fractures of the hip, spine and wrist in association with substantial morbidity and mortality and the direct costs of osteoporotic treatments appear to be rising dramatically concomitant with the increase in life expectancy (Li et al 2016). Hormone replacement therapy is the most common therapeutic approach for the prevention and treatment of postmenopausal osteoporosis, the Women’s Health Initiative reported that the health risks of hormone replacement therapy exceed its benefits (Yu et al 2016). The use of bisphosphonates for the treatment of osteoporosis has been reported (Bagan et al 2016; Eriksen et al 2014; Safer et al 2016). The potential bone-forming agents in bisphosphonates are associated with serious side effects and may not yield the expected improvements in bone quality and bone union ratio (Luhe et al 2008).
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