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人乳牙牙周膜成纤维样细胞产生基质降解酶及抑制破骨样细胞分化

Production of matrix-degrading enzymes and inhibition of osteoclast-like cell differentiation by fibroblast-like cells from the periodontal ligament of human primary teeth.

作者信息

Wu Y M, Richards D W, Rowe D J

机构信息

Department of Growth and Development, School of Dentistry, University of California-San Francisco, 94143-0754, USA.

出版信息

J Dent Res. 1999 Feb;78(2):681-9. doi: 10.1177/00220345990780020801.

DOI:10.1177/00220345990780020801
PMID:10029467
Abstract

Clinically, the most apparent difference between the primary and permanent dentitions is the physiologic loss of the primary tooth by root resorption. Root resorption is associated with loss of integrity of the periodontal ligament (PDL), followed by recruitment of resorptive cells that remove root structure. We therefore cultured primary dentition PDL fibroblasts (PPDL cells) to investigate in vitro their production of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs), and the effects of soluble factors produced by these cells on osteoclast-like cell differentiation. These studies demonstrate that PPDL cells in vitro have a heterogeneous morphology, and they constitutively synthesize 92-kDa gelatinase, 72-kDa gelatinase, and 53/57-kDa procollagenase as well as TIMP-1, -2, and a third inhibitor of matrix metalloproteinase, as determined by substrate gel zymography and immunoblot analysis. Compared with PDL cells from the permanent dentition, PPDL cells generally produced a greater amount of collagenase but similar amounts of the gelatinases and inhibitors. PPDL cells were treated with pro-inflammatory cytokines to determine their effect on the expression of matrix-degrading enzymes and inhibitors. Interleukin-1alpha and tumor necrosis factor-alpha enhanced the constitutive expression of proteinases but not that of inhibitors in PPDL cells. Conditioned media from PPDL cell lines inhibited the differentiation of osteoclast-like cells in mouse bone marrow cultures. These findings indicate that PPDL cells may modulate the cascade of root resorption both by their regulated production of proteinases and inhibitors and by synthesis of unknown soluble factor(s) that may regulate osteoclast development.

摘要

临床上,乳牙列与恒牙列最明显的区别在于乳牙通过牙根吸收而发生的生理性脱落。牙根吸收与牙周膜(PDL)完整性的丧失有关,随后募集吸收细胞来去除牙根结构。因此,我们培养了乳牙列牙周膜成纤维细胞(PPDL细胞),以体外研究它们产生基质金属蛋白酶(MMPs)和MMP组织抑制剂(TIMPs)的情况,以及这些细胞产生的可溶性因子对破骨细胞样细胞分化的影响。这些研究表明,体外培养的PPDL细胞具有异质性形态,通过底物凝胶酶谱分析和免疫印迹分析确定,它们组成性地合成92-kDa明胶酶、72-kDa明胶酶、53/57-kDa前胶原酶以及TIMP-1、-2和第三种基质金属蛋白酶抑制剂。与恒牙列的牙周膜细胞相比,PPDL细胞通常产生更多的胶原酶,但明胶酶和抑制剂的产量相似。用促炎细胞因子处理PPDL细胞,以确定它们对基质降解酶和抑制剂表达的影响。白细胞介素-1α和肿瘤坏死因子-α增强了PPDL细胞中蛋白酶的组成性表达,但没有增强抑制剂的表达。PPDL细胞系的条件培养基抑制了小鼠骨髓培养物中破骨细胞样细胞的分化。这些发现表明,PPDL细胞可能通过其对蛋白酶和抑制剂的调节性产生以及通过合成可能调节破骨细胞发育的未知可溶性因子来调节牙根吸收的级联反应。

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