Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions.
Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions.
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DOI：
10.1038/s12276-021-00710-y
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发表时间：
2021-11
影响因子：
12.8
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Cho Y;Jeong S;Kim H;Kang D;Lee J;Kang SB;Kim JH
骨关节炎（OA）是最常见的关节炎形式。它的特点是关节软骨的进行性破坏和慢性疼痛的发展，构成了相当大的社会经济负担。目前，药物治疗的主要目的是缓解与炎症和疼痛相关的OA症状。然而，随着对OA病理的了解不断增加，已经确定了几个潜在的治疗靶点，从而使疾病改善OA药物（DMOADs）得以开发。通过靶向炎性细胞因子、基质降解酶、Wnt通路和oa相关疼痛，DMOADs成功调节骨关节炎软骨的退行性改变。此外，再生方法旨在通过刺激内源性干细胞的软骨形成和软骨细胞的基质合成代谢来抵消软骨基质的损失。新兴的策略包括开发抗衰老药物或RNA疗法，以消除驱动OA的细胞或分子来源。本文综述了dmoad的发展现状以及临床前和临床试验的相关结果，并讨论了治疗OA的新兴治疗方法的潜力。研究人员正在探索几种有希望的方法来开发治疗骨关节炎的方法，以控制或逆转其进展，而不仅仅是缓解炎症和疼痛的症状。这些新的机会来自于对骨关节炎发病和进展的分子机制的进一步了解。韩国首尔国立大学的Kang Seung-Baik， Jin-Hong Kim和他们的同事回顾了已经在临床试验中显示出希望的疾病修饰策略的现状和未来方向。他们讨论了通过控制炎症信号分子、酶作用和导致软骨退化的分子途径来限制关节软骨损伤的方法。他们还考虑可以刺激受损软骨活跃再生的治疗方法。他们得出的结论是，一些方法将很快准备好进入一般临床应用。
Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA. Researchers are exploring several promising avenues to develop treatments for osteoarthritis that control or reverse its progress, rather than simply relieving the symptoms of inflammation and pain. These new opportunities are emerging from increased understanding of the molec_reular mechanisms underlying the onset and progression of osteoarthritis. Seung-Baik Kang, Jin-Hong Kim and colleagues at Seoul National University, South Korea, review the current status and future directions of disease-modifying strategies that are already showing promise in clinical trials. They discuss approaches aimed at restricting the damage to joint cartilage by controlling the inflammatory signaling molecules, enzyme actions and molecular pathways that cause cartilage to degenerate. They also consider treatments that could stimulate the active regeneration of damaged cartilage. They conclude that some approaches will soon be ready to move into general clinical use.
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影响因子：
4.9
作者：
Cohen SB;Proudman S;Kivitz AJ;Burch FX;Donohue JP;Burstein D;Sun YN;Banfield C;Vincent MS;Ni L;Zack DJ
通讯作者：
Zack DJ
影响因子：
4.9
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DOI：
10.1073/pnas.1414126111
发表时间：
2014-12-09
影响因子：
11.1
作者：
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通讯作者：
Broemme, Dieter
影响因子：
8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Greenbaum, D