Decreased Mechanical Strength and Collagen Content in SPARC-Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity.
Decreased Mechanical Strength and Collagen Content in SPARC-Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity.
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通过抑制转谷氨酰胺酶活性，可以逆转 SPARC 无效牙周膜机械强度和胶原蛋白含量的降低。
DOI：
10.1002/jbmr.2522
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Bradshaw,AmyD
中科院分区：
文献类型：
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作者：
Trombetta-eSilva,Jessica;Rosset,EmilieA;Hepfer,RGlenn;Wright,GregoryJ;Baicu,Catalin;Yao,Hai;Bradshaw,AmyD
牙周膜(PDL)是连接牙齿矿化外层和牙槽骨的重要组织。PDL主要由非矿化的纤维性胶原蛋白组成。酸性和富含半胱氨酸的分泌蛋白(SPARC/Osteonectin)是一种胶原结合的基质细胞蛋白，已被证明对PDL的胶原动态平衡是必不可少的。在没有SPARC的情况下，PDL胶原纤维比构成WT PDL的纤维更小、密度更低。本研究的目的是确定SPARC影响PDL胶原纤维组装和形态的细胞机制。纤维状胶原蛋白的交联度是影响不溶性胶原蛋白掺入和纤维形态的一个已知参数。因此，与WT小鼠(C57BL/6J)相比，在没有SPARC表达的情况下，胶原纤维的大小和数量的减少导致了磨牙拔除力的降低。此外，在SPARC缺失的PDL中，通过免疫组织化学结果支持的生化分析，发现转谷氨酰胺酶活性增加。具体地说，在PDL中，I型胶原被确定为转谷氨酰胺酶的底物，并且与WT相比，SPARC缺失的组织中I型胶原的转谷氨酰胺酶活性更高。值得注意的是，抑制SPARC缺失的PDL中的转谷氨酰胺酶活性会导致胶原纤维厚度和胶原含量的增加，而向WT小鼠注射转谷氨酰胺酶抑制剂仅导致胶原纤维厚度的增加。此外，用转谷氨酰胺酶抑制剂治疗的PDL在WT和SPARC缺失小鼠中表现出摩尔拔牙力的增加。因此，SPARC被认为是I型胶原上谷氨酰胺转氨酶活性的关键调节因子，与组织的机械强度有关。©2015美国骨与矿物研究学会
The periodontal ligament (PDL) is a critical tissue that provides a physical link between the mineralized outer layer of the tooth and the alveolar bone. The PDL is composed primarily of nonmineralized fibrillar collagens. Expression of secreted protein acidic and rich in cysteine (SPARC/osteonectin), a collagen‐binding matricellular protein, has been shown to be essential for collagen homeostasis in PDL. In the absence of SPARC, PDL collagen fibers are smaller and less dense than fibers that constitute WT PDL. The aim of this study was to identify cellular mechanisms by which SPARC affected collagen fiber assembly and morphology in PDL. Cross‐linking of fibrillar collagens is one parameter that is known to affect insoluble collagen incorporation and fiber morphology. Herein, the reduction in collagen fiber size and quantity in the absence of SPARC expression was shown to result in a PDL with reduced molar extraction force in comparison to that of WT mice (C57Bl/6J). Furthermore, an increase in transglutaminase activity was found in SPARC‐null PDL by biochemical analyses that was supported by immunohistochemical results. Specifically, collagen I was identified as a substrate for transglutaminase in PDL and transglutaminase activity on collagen I was found to be greater in SPARC‐null tissues in comparison to WT. Strikingly, inhibition of transglutaminase activity in SPARC‐null PDL resulted in increases in both collagen fiber thickness and in collagen content, whereas transglutaminase inhibitors injected into WT mice resulted in increases in collagen fiber thickness only. Furthermore, PDL treated with transglutaminase inhibitors exhibited increases in molar extraction force in WT and in SPARC‐null mice. Thus, SPARC is proposed to act as a critical regulator of transglutaminase activity on collagen I with implications for mechanical strength of tissues. © 2015 American Society for Bone and Mineral Research