Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics.
Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics.
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DOI：
10.3390/ijms22073553
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发表时间：
2021-03-29
影响因子：
5.6
通讯作者：
Rajawat J
中科院分区：
文献类型：
--
作者：
Chandra A;Rajawat J
骨是一个动态器官，由严格调节的机制维持。随着年龄的增长，由骨形成和骨吸收之间的复杂平衡维持的骨稳态经历失调。氧化应激诱导的DNA损伤、细胞凋亡和细胞衰老都是导致这种组织功能障碍和骨稳态失衡的原因。这些细胞机制已成为治疗年龄相关性骨质疏松症的治疗靶点。遗传小鼠模型已显示衰老细胞清除在减轻年龄相关性骨质疏松症中的重要性。此外，我们和其他人已经表明，靶向细胞衰老是缓解年龄和辐射诱导的骨质疏松症的有效工具。衰老细胞还具有被称为衰老相关分泌表型（SASP）的改变的分泌组，其可以具有自分泌、旁分泌或内分泌功能。目前的审查讨论了当前和潜在的途径，导致衰老的骨骼，以及如何在年龄相关的骨质疏松症骨稳态受到影响。该综述还讨论了现有的骨质疏松症治疗方法，并根据细胞衰老和SASP作为骨老化的潜在发病机制，为新的治疗选择提供了合理化。
Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis, which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in the bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Furthermore, we and others have shown that targeting cellular senescence pharmacologically was an effective tool to alleviate age- and radiation-induced osteoporosis. Senescent cells also have an altered secretome known as the senescence associated secretory phenotype (SASP), which may have autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton and how bone homeostasis is affected during age-related osteoporosis. The review has also discussed existing therapeutics for the treatment of osteoporosis and rationalizes for novel therapeutic options based on cellular senescence and the SASP as an underlying pathogenesis of an aging bone.
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影响因子：
4.3
作者：
Brennan TA;Egan KP;Lindborg CM;Chen Q;Sweetwyne MT;Hankenson KD;Xie SX;Johnson FB;Pignolo RJ
通讯作者：
Pignolo RJ
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
--
作者：
Krętowski R;Borzym-Kluczyk M;Cechowska-Pasko M
通讯作者：
Cechowska-Pasko M
影响因子：
9.8
作者：
Balemans, W;Van Den Ende, J;Van Hul, W
通讯作者：
Van Hul, W
影响因子：
5.5
作者：
Bai, Jiangtao;Wang, Yuyang;Zhu, Guoying
通讯作者：
Zhu, Guoying