椎间盘退变与细胞死亡的相关研究进展

腰椎间盘退行性变被认为是临床下腰痛的重要原因,其分子机制尚未明确.近年来,椎间盘退变的分子基础研究已经成为热门.椎间盘独特的生理结构和生物力学特性导致了它易于退变的特点.椎间盘退变开始与椎间盘细胞学行为的改变有关,包括细胞死亡的增加和细胞外基质的降解.然而,在退变椎间盘中的细胞死亡机制仍不明确,主要包括细胞凋亡和自噬.对椎间盘退变分子机制的深入研究能够为将来进一步改善和治疗椎闻盘退变打下基础.虽然椎间盘退变的生物学研究方面已经取得了一定的进展,但是椎间盘本身的生物环境对生物学治疗的发展仍具有挑战性.     

Byakangelicin inhibits IL-1β–induced mouse chondrocyte inflammation in vitro and ameliorates murine osteoarthritis in vivo

Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease, resulting in severe consequences such as chronic pain and functional disability. Owing to the complex pathology, there are currently available preventative clinical therapies for OA. Several studies have reported the potential anti-inflammatory effects of byakangelicin (BYA), a component of the Angelica dahurica root extract; however, the effects of BYA in OA remain unknown. In this study, we investigated the protective effects of BYA in interleukin (IL)-1β–induced mouse chondrocytes in vitro and on surgical destabilization in a medial meniscus (DMM) mouse OA model in vivo. In vitro, BYA treatment inhibited IL-1β–mediated inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6 expression. Moreover, BYA promoted the expression of type two collagen and aggrecan but inhibited the expression of thrombospondin motifs 5 and matrix metalloproteinases, leading to degradation of the extracellular matrix. In addition, BYA mechanistically suppressed nuclear factor-kappa B signaling in the IL-1β–induced chondrocytes. The protective effects of BYA in OA development were also observed in vivo using the DMM model. In conclusion, our results highlight BYA as a candidate for OA treatment and prevention.     

Chondroprotective activity of a detoxicated traditional Chinese medicine (Fuzi) of Aconitum carmichaeli Debx against severe-stage osteoarthritis model induced by mono-iodoacetate

Ethnopharmacological relevance: Fuzi is an effective but toxic traditional Chinese medicine (TCM) derived from Aconitum carmichaeli. In our previous study, detoxicated Fuzi (d-Fuzi) has been originally developed with no toxicity but significant efficacy. However, whether d-Fuzi can be used for therapy of osteoarthritis (OA), remain unknown.Materials and methods: Severe OA model was established by intra-articular mono-iodoacetate (MIA) injection (1.25 mg) into rats and orally treated with 2 g/ml d-Fuzi at a dosage of 7 ml/kg body weight for 28 days. In vivo, the articular radiographic and histopathologic analyses were performed to qualitatively assess the chondroprotective effect of d-Fuzi, followed by quantitative measurements of bone density and Mankin scores. In vitro, such effect on chondrocyte viability after MIA attack was evaluated. Hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS) was performed for chemical analysis of d-Fuzi.Results: d-Fuzi was demonstrated to possess chondroprotective activity on MIA-induced OA model by in vivo preventing the articular degeneration and the reducing of bone density and Mankin score, as well as by in vitro promoting the chondrocyte proliferation and inhibiting the MIA-induced chondrocyte damage. A total of 23 compounds were identified in d-Fuzi, most of which were deduced as the non-toxic derivatives of aconite alkaloids.Conclusions: This is the first report regarding chondroprotective effect and chemical profile of d-Fuzi, originally revealing its great anti-OA potential and thereby providing a promising TCM candidate for OA therapy.