Aonjittra Phanrungsuwan, Michael B Chavez, Leena A Eltilib, Tamara N Kolli, Fatma F Mohamed, Michelle H Tan, Cristiane R Salmon, Francisco H Nociti, Brian L Foster
{"title":"小鼠硬骨素缺失对牙槽骨和细胞骨水泥的不同影响。","authors":"Aonjittra Phanrungsuwan, Michael B Chavez, Leena A Eltilib, Tamara N Kolli, Fatma F Mohamed, Michelle H Tan, Cristiane R Salmon, Francisco H Nociti, Brian L Foster","doi":"10.1002/JPER.24-0025","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/β-catenin signaling expressed by osteocytes and cementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost<sup>-/-</sup>) mouse model to better understand the role of cementocytes in CC.</p><p><strong>Methods: </strong>Mandibles and femurs of Sost<sup>-/-</sup> and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry.</p><p><strong>Results: </strong>Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost<sup>-/-</sup> versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost<sup>-/-</sup> at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost<sup>-/-</sup> versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost<sup>-/-</sup> versus WT AB osteocytes, were unchanged in cementocytes.</p><p><strong>Conclusions: </strong>These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation.</p><p><strong>Plain language summary: </strong>Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.</p>","PeriodicalId":16716,"journal":{"name":"Journal of periodontology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disparate effects of sclerostin deletion on alveolar bone and cellular cementum in mice.\",\"authors\":\"Aonjittra Phanrungsuwan, Michael B Chavez, Leena A Eltilib, Tamara N Kolli, Fatma F Mohamed, Michelle H Tan, Cristiane R Salmon, Francisco H Nociti, Brian L Foster\",\"doi\":\"10.1002/JPER.24-0025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/β-catenin signaling expressed by osteocytes and cementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost<sup>-/-</sup>) mouse model to better understand the role of cementocytes in CC.</p><p><strong>Methods: </strong>Mandibles and femurs of Sost<sup>-/-</sup> and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry.</p><p><strong>Results: </strong>Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost<sup>-/-</sup> versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost<sup>-/-</sup> at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost<sup>-/-</sup> versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost<sup>-/-</sup> versus WT AB osteocytes, were unchanged in cementocytes.</p><p><strong>Conclusions: </strong>These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation.</p><p><strong>Plain language summary: </strong>Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.</p>\",\"PeriodicalId\":16716,\"journal\":{\"name\":\"Journal of periodontology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-07-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of periodontology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/JPER.24-0025\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of periodontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/JPER.24-0025","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
背景:细胞骨水泥(CC)包括骨水泥细胞,这些细胞被怀疑与骨中的成骨细胞一样调节CC的形成或吸收。Sclerostin(SOST)是一种由骨细胞和骨水泥细胞表达的Wnt/β-catenin信号转导的分泌型负调控因子。骨细胞 SOST 的表达会减少骨形成。我们使用 Sost 基因敲除(Sost-/-)小鼠模型研究了与牙槽骨(AB)相比,SOST 在 CC 中的功能重要性,以更好地了解骨水泥细胞在 CC 中的作用:方法:在出生后42天和120天(dpn)对Sost-/-小鼠和野生型(WT)小鼠的下颌骨和股骨进行分析。42 dpn时拔除双侧上颌第一磨牙,术后21天检查AB愈合(上颌磨牙窝)和CC附着(下颌第一磨牙)情况。分析包括微型计算机断层扫描、组织学和免疫组化:结果:在42和/或120 dpn时,Sost-/-与WT小鼠相比,股骨皮质骨和骨小梁以及下颌骨体积同样增加。与之前的报告相反,Sost-/-小鼠在这两个年龄段的 CC 都没有增加。我们对 AB 和 CC 进行了挑战实验,以探索组织特异性反应。Sost 基因缺失可改善拔牙后 AB 的愈合。相反,实验诱导的臼齿贴合未能刺激 Sost-/- 与 WT 小鼠相比更多的 CC 形成。Wnt 通路标记 AXIN2 和 DKK1 在 Sost-/- 相对于 WT AB 骨细胞中增加,但在骨水泥细胞中没有变化:这些数据表明,CC对SOST缺失的反应性低于AB。在研究的局限性内,这些结果并不支持骨水泥细胞是引导 CC 形成增加的关键。白话摘要:硬骨素是一种已知会抑制骨形成的蛋白质,去除硬骨素会导致更多的骨形成。骨水泥是覆盖在牙根表面的薄层。以前的研究表明,抑制硬骨素同样可以增加骨水泥的数量。我们希望比较当硬骨素缺失时骨水泥和骨的反应,以了解这两种组织之间的异同。在这项研究中,我们移除了小鼠的 Sost 基因(产生硬骨素的基因)。我们发现,没有硬骨素的小鼠腿部和下颌的骨骼更多。此外,与正常小鼠相比,没有硬骨素的小鼠在拔牙后的愈合情况也更好。令人惊讶的是,与以往的研究不同,我们发现没有硬骨素的小鼠与正常小鼠相比,骨水泥的数量并无不同。此外,我们还通过拔除对侧牙齿来挑战牙本质,使第一下颌臼齿通过形成更多的牙本质而上移。即使进行了这种挑战,我们也发现缺乏硬骨素的小鼠与正常小鼠的骨水泥数量没有差异。因此,我们在此得出结论:与骨骼相比,骨水泥对硬骨素缺失的敏感性较低。
Disparate effects of sclerostin deletion on alveolar bone and cellular cementum in mice.
Background: Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/β-catenin signaling expressed by osteocytes and cementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost-/-) mouse model to better understand the role of cementocytes in CC.
Methods: Mandibles and femurs of Sost-/- and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry.
Results: Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost-/- versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost-/- at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost-/- versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost-/- versus WT AB osteocytes, were unchanged in cementocytes.
Conclusions: These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation.
Plain language summary: Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.