BackgroundCellular 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.MethodsMandibles 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.ResultsFemur 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.ConclusionsThese 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 summarySclerostin 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.

中文翻译：

---

硬化蛋白缺失对小鼠牙槽骨和细胞牙骨质的不同影响


背景细胞牙骨质（CC）包括牙骨质细胞，这些细胞被怀疑像骨细胞中的骨细胞一样调节CC形成或吸收。硬化蛋白 (SOST) 是骨细胞和牙骨质细胞表达的 Wnt/β-连环蛋白信号传导的分泌型负调节因子。骨细胞 SOST 表达减少骨形成。我们使用以下方法研究了 SOST 在 CC 中与牙槽骨 (AB) 相比的功能重要性索斯特昏死 （索斯特−/− ）小鼠模型，以更好地了解牙骨质细胞在 CC 中的作用。方法索斯特−/−和野生型 (WT) 小鼠在出生后 42 天和 120 天 (dpn) 进行分析。 42 dpn 时双侧拔除上颌第一磨牙，并在术后 21 天检查 AB 愈合（上颌磨牙窝）和 CC 对合（下颌第一磨牙）。分析包括显微计算机断层扫描、组织学和免疫组织化学。结果股骨皮质骨、小梁骨以及下颌骨体积在索斯特−/−与 42 和/或 120 dpn 的 WT 小鼠相比。与之前的报告相比，CC 并未增加索斯特−/−在任一年龄。我们对 AB 和 CC 进行了挑战实验，以探索组织特异性反应。拔牙后 AB 愈合得到改善索斯特删除。相比之下，实验诱导的磨牙并置未能刺激 CC 形成的增加索斯特−/−与 WT 小鼠相比。 Wnt 通路标记 AXIN2 和 DKK1 在索斯特−/−与 WT AB 骨细胞相比，牙骨质细胞中没有变化。结论这些数据表明 CC 对 SOST 删除的反应不如 AB。在研究限制内，这些结果并不支持牙骨质细胞对于指导增加 CC 形成至关重要。 简单语言总结 硬化蛋白是一种已知会抑制骨形成的蛋白质，去除硬化蛋白会导致更多的骨形成。牙骨质是覆盖牙根表面的薄层。先前的研究表明，抑制硬化蛋白同样可以增加牙骨质的量。我们想要比较缺乏硬化素时牙骨质和骨的反应，以了解这两种组织之间的异同。在这项研究中，我们删除了索斯特小鼠体内的基因（产生硬化素的基因）。我们发现，没有硬化素的小鼠的腿部和下巴有更多的骨头。此外，与正常小鼠相比，没有硬化素的小鼠在拔牙后也能更好地愈合。令人惊讶的是，与之前的研究不同，我们发现没有硬化素的小鼠的牙骨质量与正常小鼠没有差异。此外，我们通过拔除相对的牙齿来挑战牙骨质，通过建立更多的牙骨质来导致第一下颌磨牙向上移动。即使面临这一挑战，我们发现缺乏硬化素的小鼠的牙骨质量与正常小鼠相比没有差异。因此，我们在此得出结论，与骨相比，牙骨质对硬化素的缺失不太敏感。