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RANKL/OPG 比值调节受损牙髓中的破牙细胞分化。

RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp.

机构信息

Oral Health Science Center, Tokyo Dental College, Tokyo, 101-0061, Japan.

Department of Orthodontics, Matsumoto Dental University, Nagano, 399-0781, Japan.

出版信息

Sci Rep. 2021 Feb 25;11(1):4575. doi: 10.1038/s41598-021-84354-y.

Abstract

Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of OPG-deficient (KO) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in OPG-KO mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.

摘要

破骨细胞的形成受到分化因子核因子-κB 配体(RANKL)与其诱饵受体护骨素(OPG)相对比例的调节。牙组织中存在的破骨样细胞称为破牙细胞,其调节因子被认为与破骨细胞相同;然而,破牙细胞调节中 RANKL/OPG 比值是否为关键因素仍不清楚。在这里,我们发现破牙细胞调节因子巨噬细胞集落刺激因子-1、RANKL 和 OPG 可在磨牙牙髓的小鼠中检测到,但 OPG 表达占主导地位。高 OPG 表达预计对破牙细胞形成具有负调节作用;然而,在 OPG 缺陷(KO)小鼠的牙髓中未检测到破牙细胞。相反,在野生型牙髓组织中观察到损伤诱导的破牙细胞样细胞,其数量在 OPG-KO 小鼠中显著增加。损伤牙髓中的 RANKL/OPG 相对比值明显高于未损伤对照牙髓。牙髓损伤增强了缺氧诱导因子-1α和-2α的表达,已知其可增加 RANKL 或减少 OPG。这些结果表明,RANKL/OPG 的相对比值对牙髓破牙细胞形成具有重要意义,OPG 表达对于维持牙髓内稳态不是必需的,但可保护牙髓免受损伤引起的破牙细胞形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c432/7907144/edc396d32ddd/41598_2021_84354_Fig1_HTML.jpg

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