No abstract

Osteoarthritis (OA) is a common disease characterized by cartilage degeneration. In recent years much attention has been paid to Traditional Chinese Medicine (TCM) since its treatments have shown efficacy for ameliorating cartilage degradation with mild side effects. Osteoking is a TCM prescription that has long been used in OA treatment. However, the exact mechanism of Osteoking are not fully elucidated. In the current study, destabilization of the medial meniscus (DMM)-induced OA mice was introduced as a wild type animal model. After 8 weeks of administration of Osteoking, histomorphometry, OARSI scoring, gait analysis, micro-CT, and immunohistochemical staining for Col2, MMP-13, TGFβRII and pSmad-2 were conducted to evaluate the chondroprotective effects of Osteoking in vivo. Further in vitro experiments were then performed to detect the effect of Osteoking on chondrocytes. TGFβRIICol2ER transgenic mice were constructed and introduced in the current study to validate whether Osteoking exerts its anti-OA effects via the TGF-β signaling pathway. Results demonstrated that in wild type DMM mice, Osteoking ameliorated OA-phenotype including cartilage degradation, subchondral bone sclerosis, and gait abnormality. Col2, TGFβRII, and pSmad-2 expressions were also found to be up-regulated after Osteoking treatment, while MMP-13 was down-regulated. In vitro, the mRNA expression of MMP-13 and ADAMTS5 decreased and the mRNA expression of Aggrecan, COL2, and TGFβRII were up-regulated after the treatment of Osteoking in IL-1β treated chondrocytes. The additional treatment of SB505124 counteracted the positive impact of Osteoking on primary chondrocytes. In TGFβRIICol2ER mice, spontaneous OA-liked phenotype was observed and treatment of Osteoking failed to reverse the OA spontaneous progression. In conclusion, Osteoking ameliorates OA progression by decelerating cartilage degradation and alleviating subchondral bone sclerosis partly via the TGF-β signaling pathway.

Postmenopausal osteoporosis (PMOP) is a type of bone metabolism disease-related to estrogen deficiency with an increasing incidence. Traditional Chinese (TCM) has always been used and showed effectiveness in treating PMOP. In the current study, Bu-Yang herbs were considered to be the most frequently used and efficient TCM herbs in PMOP treatment. However, chemical and pharmacological profiles were not elucidated. Network pharmacology was conducted on representative Bu-Yang herbs (Yin-Yang-Huo. Du-Zhong, Bu-Gu-Zhi, Tu-Si-Zi) to investigate the mechanism of Bu-Yang herbs on PMOP. Chemical compounds, potential targets, and disease related genes were available from the corresponding database. Results showed that Bu-Yang herbs could interact with ESR1 and estrogen signaling pathways. For further validation, the Bu-Yang decoction (BYD), formula consisted of the above-mentioned 4 Bu-Yang herbs was presented for experimental validation. In vivo, BYD significantly reversed ovariectomy (OVX)-induced osteoporosis progress in a dose-dependent manner by up-regulation of bone mineral density and amelioration of bone microarchitecture. In vitro, BYD dramatically improved the proliferation and mineral nodules formation of osteoblasts. Both in vitro and in vivo results illustrated that the phenotype change induced by BYD is correlated with up-regulated of ESR1 and activation of the β-catenin pathway. Meanwhile, inhibition of ESR1 by ICI182, 780 blocked the osteogenic phenotype and β-catenin pathway activation induced by BYD. In conclusion, the current study suggested that Bu-Yang herbs are the most useful TCM herbs in treating PMOP. Furthermore, the integrated strategy of network pharmacology prediction with experimental validation suggested that BYD exerted its anti-PMOP via ESR1 and the downstream mechanism might be activation of the β-catenin signaling pathway.

Background: Shen-sui-tong-zhi formula (SSTZF) has been used to treat osteoporosis for decades and shows excellent clinical efficacy. This article aims to explore the optimal anti-osteoporotic ingredient and its precise mechanisms in mice models.Methods: In this study, we first screened the optimal anti-osteoporosis fraction of SSTZF extract in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old female C57BL/6J mice were administrated with each fraction of SSTZF. At 10 weeks after ovariectomy (OVX), femurs were collected for tissue analyses, including histology, micro-CT, biomechanical tests, and immunohistochemistry for ALP, FABP4, and β-catenin. Additionally, we also evaluated the mRNA expression level of ALP and FABP4 and the protein expression level of β-catenin after being treated with SSTZF extract in C3H10T1/2 cells. Moreover, we investigated the anti-osteoporosis effect of SSTZF extract on mice with β-catenin conditional knockout in growth plate chondrocytes (β-cateninGli1ER mice) through μCT, histology, and immunohistochemistry analyzes.Results: At 10 weeks after treatment, osteoporosis-like phenotype were significantly ameliorated in SSTZF n-butanol extract (SSTZF-NB) group mice, as indicated by increased trabecular bone area and ALP content, and decreased lipid droplet area and FABP4 content. No such improvements were observed after being treated with other extracts, demonstrating that SSTZF-NB is the optimal anti-osteoporosis fraction. Additionally, the elevated β-catenin was revealed in both OVX mice and C3H10T1/2 cells with SSTZF-NB administered. Furthermore, a significant osteoporosis-like phenotype was observed in β-cateninGli1ER mice as expected. However, SSTZF-NB failed to rescue the deterioration in β-cateninGli1ER mice, no significant re-upregulated ALP and downregulated FABP4 were observed after being treated with SSTZF-NB, demonstrating that SSTZF-NB prevents bone loss mainly via β-catenin signaling.Conclusion: SSTZF-NB enhances osteogenesis mainly via activation of β-catenin signaling in growth plate chondrocytes. SSTZF-NB is the optimal anti-osteoporosis fraction of SSTZF and it can be considered a salutary alternative therapeutic option for osteoporosis.

GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune system disease that mainly affects joints throughout the body, causing joint pain, deformity, and even disability. The use of Chinese herbal medicine (CHM) to treat RA has achieved certain effects, and Duohuo Jisheng decoction (DHJSD) is one of them. But there is no high-level evidence to support this result. The purpose of this work is to evaluate the effectiveness of DHJSD combined with DMARDs compared with isolated DMARDs for RA. Methods: We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to October 2020. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. Results: This study will evaluate the efficacy and safety of DHJSD combined with DMARDs compared with isolated DMARDs in the treatment of Rheumatoid arthritis, to provide high-quality, evidence-based clinical recommendations. Conclusion: This study will provide reliable evidence on whether Duhuo Jisheng decoction combined with DMARDs compared with isolated DMARDs is more effective in treating RA. Trial registration number: INPLASY2020100089.

Background: Knee osteoarthritis (KOA) often causes joint pain, weakness and mobility disorders, which seriously affects people’s daily life and makes them unable to work and study normally. Traditional Chinese medicine (TCM) prescription Danggui Sini Decoction (DGSND) has been widely used in clinical practice and achieved good results. But there is no high-level evidence to support this result. The aim of this study is to evaluate DGSND’s efficacy and safety in the management of KOA. Methods: We will search 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to September 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. Results: This study will compare the effects of DGSND and any other different methods on patients with KOA to provide high-quality, evidence-based clinical recommendations. Conclusion: The study provides a trustable clinical foundation for DGSND in the treatment of KOA.

Background. The Jiawei Yanghe decoction (JWYHD) is a traditional Chinese medicine formula for the treatment of osteoporosis, but its therapeutic mechanism has not been fully elucidated, and the therapeutic target of the intervention disease needs to be further verified. The dysfunction of bone mesenchymal stem cells (BMSCs) is considered to be an important pathogenesis of postmenopausal osteoporosis (PMOP). The purpose of this study was to explore how JWYHD regulates BMSC differentiation through the BMP-SMAD signal pathway. Methods. In the in vivo study, we used an ovariectomized PMOP rat (n = 36, 2-month-old, 200 ± 20 g) model and femur micro-CT analysis to study the effect of JWYHD on bone loss in rats. By immunofluorescence, the translocation expression of BMP2, a key protein in the pathway, was detected. Serum bone metabolism was detected by an enzyme-linked immunosorbent assay (ELISA). Alkaline phosphatase (ALP) activity was detected by alkaline phosphatase staining (ALPS), osteogenesis and matrix mineralization were detected by alizarin red staining (ARS), the adipogenic ability of BMSCs was detected by oil red staining (ORS), and CFU is used to detect the ability of cells to form colonies. The expression of related proteins was detected by western blotting. Results. In vivo and in vitro, the OP phenotypes of SD rats induced by ovariectomy (OVX) included impaired bone mineral density and microstructure, abnormal bone metabolism, and impaired MSC differentiation potential. JWYHD treatment reversed this trend and restored the differentiation potential of MSCs. JWYHD medicated serum and direct intervention of drugs activated the BMP-SMAD signaling pathway, promoted the osteogenic differentiation of BMSCs, and inhibited their adipogenic differentiation. Conclusions. Our data identified that JWYHD is an effective alternative drug for the treatment of PMOP that functions to stimulate the differentiation of BMSCs into osteoblasts in the BMP-SMAD signaling-dependent mechanism.