Phanrungsuwan Aonjittra, Chavez Michael B, Eltilib Leena A, Kolli Tamara N, Mohamed Fatma F, Tan Michelle H, Salmon Cristiane R, Nociti Francisco H, Foster Brian L
Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, Ohio, USA.
College of Dentistry, University of Iowa, Iowa City, Iowa, USA.
J Periodontol. 2025 Jan;96(1):82-96. doi: 10.1002/JPER.24-0025. Epub 2024 Jul 16.
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.
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.
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.
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.
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.
细胞性牙骨质（CC）包含牙骨质细胞，这类细胞被怀疑像骨中的骨细胞一样可调节CC的形成或吸收。硬化蛋白（SOST）是一种由骨细胞和牙骨质细胞分泌的Wnt/β-连环蛋白信号通路的负调节因子。骨细胞SOST表达减少会降低骨形成。我们使用Sost基因敲除（Sost）小鼠模型，研究了SOST在CC中与牙槽骨（AB）相比的功能重要性，以更好地理解牙骨质细胞在CC中的作用。
在出生后42天和120天（dpn）对Sost和野生型（WT）小鼠的下颌骨和股骨进行分析。在42 dpn时双侧拔除上颌第一磨牙，并在术后21天检查AB愈合情况（上颌磨牙牙槽窝）和CC附着情况（下颌第一磨牙）。分析包括微型计算机断层扫描、组织学和免疫组织化学。
在42和/或120 dpn时，Sost小鼠的股骨皮质骨和小梁骨以及下颌骨体积与WT小鼠相比同样增加。与之前的报道相反，在这两个年龄段，Sost均未使CC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基因缺失改善了拔牙后的AB愈合。相比之下，在Sost小鼠与WT小鼠中，实验诱导的磨牙附着未能刺激CC形成增加。Wnt通路标志物AXIN2和DKK1在Sost小鼠与WT小鼠的AB骨细胞中增加，但在牙骨质细胞中未改变。
这些数据表明CC对SOST缺失的反应比AB小。在本研究的局限性范围内，这些结果不支持牙骨质细胞对指导CC形成增加至关重要的观点。
硬化蛋白是一种已知可抑制骨形成的蛋白质，去除硬化蛋白会导致更多骨形成。牙骨质是覆盖牙根表面的薄层。先前的研究表明，抑制硬化蛋白可同样增加牙骨质的量。我们想比较硬化蛋白缺失时牙骨质和骨的反应，以了解这两种组织之间的异同。在本研究中，我们在小鼠中去除了Sost基因（产生硬化蛋白的基因）。我们发现没有硬化蛋白的小鼠腿部和颌部有更多的骨。此外，与正常小鼠相比，没有硬化蛋白的小鼠拔牙后愈合也更好。令人惊讶的是，与先前的研究不同，我们发现没有硬化蛋白的小鼠与正常小鼠相比，牙骨质的量没有差异。此外，我们通过拔除对侧牙齿来挑战牙骨质，以使第一下颌磨牙通过形成更多牙骨质向上移动。即使有这种挑战，我们发现缺乏硬化蛋白的小鼠与正常小鼠相比，牙骨质的量没有差异。因此，我们在此得出结论，与骨相比，牙骨质对硬化蛋白缺失不太敏感。
