An inulin-type fructan (AMP1-1) from Atractylodes macrocephala with anti-weightlessness bone loss activity.

LncRNA XIST facilitates S1P-mediated osteoclast differentiation via interacting with FUS

Aim: This study aims to investigate whether long noncoding RNA (lncRNA) X-inactive specific transcript (Xist) can regulate osteoclast differentiation in osteoporosis and the mechanism. Materials & methods: The mouse model of osteoporosis was established by ovariectomy surgery. Osteoclast differentiation from RAW264.7 cells was induced in vitro. The relationships between associated genes were assessed. Results: Xist and Tgif2 were upregulated, but miR-590-3p was downregulated in ovariectomy mouse femurs and cell models. Xist knockdown or miR-590-3p overexpression inhibited Tgif2 expression and osteoclast differentiation. Tgif2 and Xist were the targets of miR-590-3p. Increased miR-590-3p expression inhibited Tgif2 level and osteoclast differentiation, while Xist overexpression reversed these effects. Conclusion: Xist serves as a ceRNA of miR-590-3p to promote Tgif2 level; thereby, contributing to osteoclast differentiation.

LncRNA X inactive-specific transcript promotes osteoclast differentiation through Tgif2 by acting as a ceRNA of miR-590-3p in a murine model.

Postmenopausal osteoporosis is caused by an imbalance between osteoclasts and osteoblasts and causes severe bone loss. Osteoporotic medicines are classified into bone resorption inhibitors and bone formation promoters according to the mechanism of action. Long-term use of bisphosphonate and selective estrogen receptor modulators (SERMs) can cause severe side effects in postmenopausal osteoporosis patients. Therefore, it is important to find alternative natural products that reduce osteoclast activity and increase osteoblast formation. Sparganii Rhizoma (SR) is the dried tuberous rhizome of Sparganium stoloniferum Buchanan-Hamilton and is called “samreung” in Korea. However, to date, the effect of SR on osteoclast differentiation and the ovariectomized (OVX)-induced bone loss model has not been reported. In vitro, tartrate-resistant acid phosphatase (TRAP) staining, western blots, RT-PCR and other methods were used to examine the effect of SR on osteoclast differentiation and osteoblasts. In vivo, we confirmed the effect of SR in a model of OVX-induced postmenopausal osteoporosis. SR inhibited osteoclast differentiation and decreased the expression of TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells 1 (NFATc1) and c-Fos pathway. In addition, SR stimulates osteoblast differentiation and increased protein expression of the bone morphogenetic protein 2 (BMP-2)/SMAD signaling pathway. Moreover, SR protected against bone loss in OVX-induced rats. Our results appear to advance our knowledge of SR and successfully demonstrate its potential role as a osteoclastogenesis-inhibiting and osteogenesis-promoting herbal medicine for the treatment of postmenopausal osteoporosis.

Effects of Sparganii Rhizoma on Osteoclast Formation and Osteoblast Differentiation and on an OVX-Induced Bone Loss Model

This study aimed to evaluate the potential toxicity of a recently developed and clinically used No-Pain pharmacopuncture (NPP) solution. We also assessed the lethal dose of the NPP agent following a single intramuscular injection in Sprague-Dawley (SD) rats.Animals were divided into two groups the NPP test material group and the normal saline control group. A single intramuscular injection of the NPP agent (1.0 mL/animal) was administered to rats of the NPP test material group. The control group rats received the same volume of normal saline. Both female and male rats were included in each group. All rats were monitored for clinical signs and body weight changes for 14 days after administration of the test substance or saline. At the end of the observation period, a gross necropsy was conducted and localized tolerance at the injection site was analyzed.No mortality was observed in the NPP test material and control groups. Moreover, no test substance-related effects were observed on clinical signs, body weight, necropsy findings, and localized tolerance at the injection site.The approximate lethal dose of the NPP agent is greater than 1.0 mL/animal under the conditions used in this study. Additional toxicity evaluations and clinical studies are needed to confirm the safety of NPP use in clinical practice. 

Single-Dose Intramuscular Toxicity Test Using No-Pain Pharmacopuncture in Sprague–Dawley Rats

Osteoporosis is related to the number and activity of osteoclasts. The goal of the present study was to demonstrate the effect of Chaenomelis Fructus (CF) on osteoclastogenesis and its mechanism of bone loss prevention in an OVX-induced osteoporosis model. Osteoclasts were induced by RANKL in RAW 264.7 cells. TRAP assay was performed to measure the inhibitory effect of CF on osteoclast differentiation. Then, Expression of nuclear factor of activated T-cells (NFATc1), c-Fos which are essential transcription factors in osteoclastogenesis were detected using western blot and RT-PCR. The osteoclast-related markers were measured by RT-PCR. Moreover, the ability of CF to inhibit bone loss was researched by ovariectomized (OVX)-induced osteoporosis. Cell experiments showed that CF inhibited osteoclast differentiation and its function. Immunoblot analyses demonstrated that CF suppressed osteoclastogenesis through the NFATc1 and c-Fos signaling pathways. RT-PCR determined that CF inhibited osteoclast-related markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTK), osteoclast-associated immunoglobulin-like receptor (OSCAR), ATPase H+ Transporting V0 Subunit D2 (ATP6v0d2) and carbonic anhydrase II (CA2). In animal experiments, CF showed an inhibitory effect on bone density reduction through OVX. Hematoxylin and eosin (H&E) staining analysis data showed that CF inhibited OVX-induced trabecular area loss. TRAP staining and immunohistochemical staining analysis data showed that CF displayed an inhibitory effect on osteoclast differentiation through NFATc1 inhibition in femoral tissue. Based on the results of in vivo and in vitro experiments, CF inhibited the RANKL-induced osteoclasts differentiation and its function and effectively ameliorated OVX-induced osteoporosis rats.

/pdf/chaenomelis-fructus-inhibits-osteoclast-differentiation-by-esovf4vewv.pdf

Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis

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Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis