ABSTRACT
AIM: To evaluate the effects and medication safety of Duhuo Jisheng Decoction (DHJSD) alone or as a combination therapy with other interventions on the related clinical index in postmenopausal osteoporosis condition. METHODS: Search in CNKI, WanFang, CBM, VIP, PubMed, EMBASE, and Cochrane Library databases and randomized controlled trials where at least one group received any form of DHJSD for postmenopausal osteoporosis condition. Risk of bias was based on the Cochrane handbook, the quality of evidence was assessed by the GRADEpro online, and analyses were performed by RevMan 5.3 software. RESULTS: Eight studies were enrolled with 650 participants. DHJSD alone or with other interventions had a significant effect on BMD of the lumbar spine (MD = 0.46, 95%CI (0.24, 0.68), P < 0.0001), E2 (SMD = 0.49, 95%CI (0.30, 0.68), P < 0.0001), and clinical effectiveness (OR = 5.07, 95%CI (3.07, 8.35), P < 0.0001). However, no effect at BGP (MD = -0.84, 95%CI (-1.69, 0.00), P=0.05) was seen. CONCLUSION: The pooled estimate suggested that DHJSD combined with conventional medical therapies has a certain clinical curative effect on postmenopausal osteoporosis. However, considering the unsatisfactory quality of included trials, more high-quality trials are needed to elucidate this issue.
ABSTRACT
Effect of raloxifene (RLF) on the improvement of inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) resulted from tumor necrosis factor-α (TNF-α) induction, thus alleviating the progression of osteoporosis (OP), was investigated. An in vivo OP rat model was constructed by performing the procedures of ovariectomy (OVX). Rats were randomly divided into sham group, OVX group and RLF+OVX group. BMSCs were extracted from healthy rats, and randomly divided into control group, TNF-α group, RLF group and TNF-α+RLF group. Viability and cellular calcification ability in each group were detected. The relative levels of osteocalcin (OCN), Runx2 and NF-κB in cells with different treatments were determined. The body weight of rats in the OVX group and RLF+OVX group gradually increased compared with that in the sham group on the 8th week. No significant difference in body weight was observed between the rats of the OVX group and RLF+OVX group. Bone metabolism index (BMD) in the rats of the RLF+OVX group was higher than that of the OVX group, and lower compared with that of the sham group. Compared with the sham group, the elastic/max radial degree and elastic/max load of femora were reduced in the OVX group and RLF+OVX group, especially in the OVX group. The relative levels of OCN and Runx2, as well as the ALP activity and calcification ability, were decreased in the OVX group compared with the sham group, and the effect was partially reversed by the RLF treatment. After osteogenic differentiation of BMSCs, the viability and calcification ability were markedly reduced in TNF-α group, which was reversed by RLF treatment. Moreover, TNF-α induction downregulated the relative levels of OCN and Runx2, and RLF treatment could enhance their levels. The upregulated NF-κB protein level, induced by TNF-α, was reduced after RLF treatment. TNF-α induction inhibits osteogenic differentiation of BMSCs, which could be remarkably alleviated by RLF. It is suggested that RLF contributes to the alleviation of OP progression.
ABSTRACT
This study aimed to investigate whether X inactivate-specific transcript (XIST) regulated the expression of tissue non-specific alkaline phosphatase (ALPL) through miR-9-5p to promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). We elucidated the molecular regulation mechanisms of XIST underlying osteogenic differentiation of hBMSCs. In osteoporotic patients with hBMSCs, the expression of miR-9-5p was upregulated and the expression of XIST was downregulated. When hBMSCs were treated with osteogenic induction, the expression of XIST was increased and the expression of miR-9-5p was decreased. The osteogenic differentiation of hBMSCs was significantly decreased after knocking down XIST. Luciferase analysis revealed that XIST could directly bind to miR-9-5p and exert a negative regulatory effect on its expression. MiR-9-5p could bind directly to the 3'-UTR of ALPL and inhibit the expression of ALPL. Knockout of XIST reduced the expression of ALPL, while co-transfection of the miR-9-5p inhibitor could reverse the expression of the ALPL gene. In hBMSCs, overexpression of XIST upregulated the expression of ALPL, but the miR-9-5p mimic could reverse the expression of ALPL. Furthermore, silencing of ALPL could downregulate the expression of osteopontin(OPN) and osteocalcin(OCN) induced by miR-9-5p inhibitors. In conclusion, XIST regulated the expression of ALPL by targeting miR-9-5p. It could be used as a positive regulator of osteogenic differentiation of hBMSC.
