Deficiency of Trps1 in Cementoblasts Impairs Cementogenesis and Tooth Root Formation.

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Calcified Tissue International Pub Date : 2024-11-01 Epub Date: 2024-08-23 DOI:10.1007/s00223-024-01277-2
Kaoru Fujikawa, Mairobys Socorro, Lyudmila Lukashova, Priyanka Hoskere, Paulina Keskinidis, Kostas Verdelis, Dobrawa Napierala
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引用次数: 0

Abstract

Cementum is the least studied of all mineralized tissues and little is known about mechanisms regulating its formation. Therefore, the goal of this study was to provide new insights into the transcriptional regulation of cementum formation by determining the consequences of the deficiency of the Trps1 transcription factor in cementoblasts. We used Trps1Col1a1 cKO (2.3Co1a1-CreERT2;Trps1fl/fl) mice, in which Trps1 is deleted in cementoblasts. Micro-computed tomography analyses of molars of 4-week-old males and females demonstrated significantly shorter roots with thinner mineralized tissues (root dentin and cementum) in Trps1Col1a1 cKO compared to WT mice. Semi-quantitative histological analyses revealed a significantly reduced area of cellular cementum and localized deficiencies of acellular cementum in Trps1Col1a1 cKO mice. Immunohistochemical analyses revealed clustering of cementoblasts at the apex of roots, and intermittent absence of cementoblasts on Trps1Col1a1 cKO cementum surfaces. Fewer Osterix-positive cells adjacent to cellular cementum were also detected in Trps1Col1a1 cKO compared to WT mice. Decreased levels of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme required for proper cementogenesis, were apparent in cementum, periodontal ligament, and alveolar bone of Trps1Col1a1 cKO. There were no apparent differences in levels of bone sialoprotein (Bsp) in cementum. Quantitative analyses of picrosirius red-stained periodontal ligament revealed shorter and disorganized collagen fibers in Trps1Col1a1 cKO mice demonstrating impaired periodontal structure. In conclusion, this study has identified Trps1 transcription factor as one of the important regulators of cellular and acellular cementum formation. Furthermore, this study suggests that Trps1 supports the function of cementoblasts by upregulating expression of the major proteins required for cementogenesis, such as Osterix and TNAP.

Abstract Image

骨水泥母细胞中的 Trps1 缺乏会影响骨水泥生成和牙根形成
骨水泥是所有矿化组织中研究最少的一种,人们对其形成的调控机制知之甚少。因此,本研究的目的是通过确定骨水泥母细胞中 Trps1 转录因子缺乏的后果,为骨水泥形成的转录调控提供新的见解。我们使用了Trps1Col1a1 cKO(2.3Co1a1-CreERT2;Trps1fl/fl)小鼠,在这种小鼠中,骨水泥母细胞中的Trps1被缺失。对 4 周大雄性和雌性小鼠臼齿的显微计算机断层扫描分析表明,与 WT 小鼠相比,Trps1Col1a1 cKO 小鼠的牙根明显较短,矿化组织(牙本质和骨水泥)较薄。半定量组织学分析表明,Trps1Col1a1 cKO 小鼠的细胞骨水泥面积明显减少,局部缺失无细胞骨水泥。免疫组化分析表明,牙根顶端有成群的骨水泥母细胞,Trps1Col1a1 cKO 小鼠的骨水泥表面间歇性缺乏骨水泥母细胞。与 WT 小鼠相比,Trps1Col1a1 cKO 小鼠邻近细胞骨水泥的 Osterix 阳性细胞也较少。在 Trps1Col1a1 cKO 小鼠的骨水泥、牙周韧带和牙槽骨中,组织非特异性碱性磷酸酶(TNAP)水平明显下降,而 TNAP 是正常骨水泥生成所需的一种酶。骨水泥中的骨硅蛋白(Bsp)水平没有明显差异。对皮色红染色的牙周韧带进行定量分析发现,Trps1Col1a1 cKO 小鼠的胶原纤维较短且杂乱无章,表明牙周结构受损。总之,本研究发现 Trps1 转录因子是细胞和无细胞骨水泥形成的重要调节因子之一。此外,本研究还表明,Trps1 通过上调骨水泥形成所需的主要蛋白(如 Osterix 和 TNAP)的表达,支持骨水泥母细胞的功能。
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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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