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Abstract：
Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet®, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet®, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.
摘要：
骨关节炎(OA)是一种引起慢性疼痛的慢性退行性关节疾病,肿胀,刚度,残疾,并显著降低生活质量。通常,使用止痛药和非甾体抗炎药（NSAID）治疗OA。虽然目前的药物治疗很常见，它们潜在的副作用促使人们探索功能性膳食补充剂。最近,由于蛋壳膜（ESM）在缓解关节疼痛和僵硬方面的临床功效，因此已成为关节和结缔组织疾病的潜在功能成分。尽管有很好的临床证据,ESM对OA进展的影响及其作用机制尚不清楚。这项研究评估了Ovomet®的疗效，粉状天然ESM，在碘乙酸钠（MIA）诱导的小鼠和大鼠OA啮齿动物模型中预防关节疼痛和疾病进展。结果表明,在OA诱导前5天和之后28天接受口服补充的小鼠和大鼠中,ESM显著缓解关节疼痛并减弱关节软骨破坏。有趣的是,ESM显著抑制肿瘤坏死因子α(TNF-α)等促炎细胞因子的mRNA表达,白细胞介素-1β（IL-1β），和白细胞介素-6（IL-6），以及炎症介质，环氧合酶-2（COX-2），OA早期膝关节软骨中的诱导型一氧化氮合酶，OA诱导后7天内。然而,在OA诱导后28天的晚期未观察到这种效应.ESM进一步减弱软骨降解酶如基质金属蛋白酶（MMPs）3和13以及具有血小板反应蛋白基序5（ADAMTS-5）的整合素和金属蛋白酶的蛋白质表达的诱导，在后期阶段。此外,MIA诱导的软骨成分的蛋白质表达水平的降低，软骨寡聚基质蛋白（COMP），聚集蛋白聚糖(ACAN)和II型胶原蛋白α-1链(COL2α1)，通过ESM治疗，软骨组织中促进软骨细胞外基质（ECM）合成的转录因子SRY-Box9（SOX-9）增加。我们的研究结果表明Ovomet®，一种天然的ESM粉末，是一种有前途的饮食功能成分，可以减轻疼痛，炎症反应，和与OA进展相关的软骨退化。
