RANKL and RANK in extracellular vesicles: surprising new players in bone remodeling.
RANKL and RANK in extracellular vesicles: surprising new players in bone remodeling.
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DOI：
10.20517/evcna.2020.02
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Rody WJ Jr
中科院分区：
文献类型：
--
作者：
Holliday LS;Patel SS;Rody WJ Jr
核因子κ b配体受体激活剂（RANKL）及其受体RANK和结合RANKL并作为可溶性诱饵受体的骨保护素是骨重塑的重要控制者。它们在建立免疫耐受以及淋巴系统和乳腺的发育中也起着重要作用。在骨中，RANKL通过将RANK与破骨细胞前体和破骨细胞结合来刺激破骨细胞的形成。这是骨吸收所必需的。最近，RANKL和RANK被证明是细胞外囊泡（EVs）的功能成分。本文回顾了ev中RANKL和RANK与生物调控作用的数据联系，并对关键的未解问题进行了研究。RANKL和RANK是跨膜蛋白，它们在电动汽车中的存在使它们能够在远离其起源细胞的距离上发挥作用。由于携带rankl的骨细胞和成骨细胞在体内通常与含有rankl的破骨细胞在空间上距离较远，这可能对刺激破骨细胞形成和骨吸收至关重要。来自破骨细胞的ev中的RANK能够刺激成骨细胞中的RANKL反向信号通路，从而促进骨形成。这有助于骨吸收与骨形成的耦合，并激发了新的双功能治疗剂。血清中含有RANKL和RANK的ev可作为骨和免疫病理的生物标志物。综上所述，含有RANKL和RANK的ev已被确定为骨生物学中的细胞间调节因子。它们增加了负责维持骨骼的中央信号网络的复杂性。RANKL-和含有RANKL的ev作为药物靶点和生物标志物具有很大的吸引力。
Receptor activator of nuclear factor kappa B-ligand (RANKL), its receptor RANK, and osteoprotegerin which binds RANKL and acts as a soluble decoy receptor, are essential controllers of bone remodeling. They also play important roles in establishing immune tolerance and in the development of the lymphatic system and mammary glands. In bone, RANKL stimulates osteoclast formation by binding RANK on osteoclast precursors and osteoclasts. This is required for bone resorption. Recently, RANKL and RANK have been shown to be functional components of extracellular vesicles (EVs). Data linking RANKL and RANK in EVs to biological regulatory roles are reviewed, and crucial unanswered questions are examined. RANKL and RANK are transmembrane proteins and their presence in EVs allows them to act at a distance from their cell of origin. Because RANKL-bearing osteocytes and osteoblasts are often spatially distant from RANK-containing osteoclasts in vivo, this may be crucial for the stimulation of osteoclast formation and bone resorption. RANK in EVs from osteoclasts has the capacity to stimulate a RANKL reverse signaling pathway in osteoblasts that promotes bone formation. This serves to couple bone resorption with bone formation and has inspired novel bifunctional therapeutic agents. RANKL- and RANK- containing EVs in serum may serve as biomarkers for bone and immune pathologies. In summary, EVs containing RANKL and RANK have been identified as intercellular regulators in bone biology. They add complexity to the central signaling network responsible for maintaining bone. RANKL- and RANK-containing EVs are attractive as drug targets and as biomarkers.
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
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发表时间：
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期刊：
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影响因子：
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