Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.
Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.
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DOI：
10.21037/qims-23-254
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发表时间：
2023-09-01
影响因子：
2.8
通讯作者：
中科院分区：
文献类型：
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作者：
类风湿关节炎(RA)是一种导致慢性关节炎症的自身免疫性疾病。骨侵蚀是类风湿关节炎最严重的病理状态，也是导致关节畸形和残疾的主要原因。蜂毒素穴位注射是治疗类风湿关节炎的一种有效的中医方法。本研究旨在探讨MAI对RA骨侵蚀的影响及其机制。建立胶原性关节炎(CIA)小鼠模型作为实验对象。给CIA小鼠隔日给药一次，连续给药28天。通过体重、关节炎指数(AI)、肿胀关节计数(SJC)和后爪厚度来评价MAI对关节疾病的影响。通过微型计算机断层扫描(Micro-CT)获取踝关节的放射学改变，并通过病理染色观察组织学改变。检测脏器组织学改变、脾指数、血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和肌酐(Crea)水平，以评价MAI的毒性。采用酶联免疫吸附试验(EL ISA)检测细胞因子的表达水平，评价CIA小鼠的免疫功能。MAI能明显改善小鼠CIA的临床症状，包括后爪厚度、AI和足关节肿胀数(多数为P<0.05或P<0.01)。根据组织病理学分析，MAI可减轻炎症细胞浸润、滑膜增生、血管疙瘩形成和骨侵蚀(均P<；0.01)。Micro-CT和抗酒石酸酸性磷酸酶(TRAP)染色(P<；0.01)也显示MAI可以通过减少破骨细胞的形成来减轻骨侵蚀。MAI不仅能减轻免疫增强作用[高剂量组P<；0.05]，而且无肝肾副作用(P>；0.05)。此外，还能降低血清IL-6和肿瘤坏死因子-α水平，升高血清IL-4和IL-10水平(多数P<0.05或P<0.01)，降低肿瘤坏死因子-α水平。转录组测序结果表明，MAI影响破骨细胞分化途径基因的表达，这与核因子κB配体/核因子kappaB受体激活物(RANKL/NF-κB)途径有关。根据我们的研究结果，MAI可以抑制关节炎症，抑制RANKL/NF-κB介导的破骨细胞分化，以挽救CIA小鼠的骨侵蚀，提示MAI可能是一种潜在的RA治疗物质。
Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. Bone erosion is the most serious pathological condition of RA and the main cause of joint deformities and disability. Melittin acupoint injection (MAI) is an effective traditional Chinese medicine (TCM) method for RA treatment. This study aimed to investigate the effect of MAI on RA bone erosion and to elucidate the underlying mechanism. A collagen-induced arthritis (CIA) mouse model was established as the experimental subject. MAI was administrated once every other day for 28 days to mice with CIA. The effects of MAI on joint diseases were assessed by body weight, arthritis index (AI) score, swollen joint count (SJC) score, and hind paw thickness. Ankle radiological changes were captured by micro-computed tomography (micro-CT) and histological changes were observed by pathological staining. Organ histological changes, spleen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Crea) levels of serum were tested to evaluate the toxicity of MAI. Cytokine expression levels were confirmed by enzyme-linked immunosorbent assay (ELISA) to evaluate the immunity of CIA mice. MAI administration markedly improved the clinical signs of CIA in mice, including hind paw thickness, AI, and the number of swollen paw joints (most of them P<0.05 or even <0.01). According to histopathological analysis, MAI ameliorated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone erosion (all P<0.01). Micro-CT and tartrate-resistant acid phosphatase (TRAP) staining (P<0.01) also revealed that MAI could relieve bone erosion via reducing the formation of osteoclasts. Not only could MAI relieve the immunological boost [P<0.05 for the high-dose MAI (HM) group], but also it had no liver or kidney side effects (P>0.05). In addition, it decreased the serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) and increased the serum levels of IL-4 and IL-10 (the majority of P<0.05 or even <0.01). Transcriptome sequencing results indicated that MAI affected the expression of osteoclast differentiation pathway genes, which was connected with the receptor activator of the nuclear factor κB ligand/nuclear factor kappa B (RANKL/NF-κB) pathway. Based on our findings, MAI could suppress joint inflammation and inhibit RANKL/NF-κB-mediated osteoclast differentiation to rescue bone erosion in CIA mice, suggesting that MAI can be a potentially therapeutic substance for RA.
影响因子：
4.6
作者：
Kavitha, Chandagirikoppal V.;Deep, Gagan;Gangar, Subhash C.;Jain, Anil K.;Agarwal, Chapla;Agarwal, Rajesh
通讯作者：
Agarwal, Rajesh