Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Department of Oral and Maxillofacial Surgery, University Hospital RWTH Aachen, RWTH Aachen University, 52074 Aachen, Germany.
Int J Mol Sci. 2021 Jan 7;22(2):539. doi: 10.3390/ijms22020539.
Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α- and β-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α- and β-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α- and β-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.
一氧化氮（NO）与可溶性鸟苷酸环化酶（sGC）结合，在还原氧化的血红素铁状态下激活它，并生成环鸟苷酸（cGMP），导致血管舒张和破骨细胞活性抑制。在炎症中，sGC 被氧化，对 NO 变得不敏感。NO 和血红素非依赖性激活 sGC 需要α-和β-亚基的蛋白表达。牙周炎的炎症诱导破牙骨质细胞吸收牙骨质和破骨细胞吸收牙槽骨，这可能导致牙齿脱落。由于破牙骨质细胞中存在 sGC 尚不清楚，我们使用 CD68 和组织蛋白酶 K 的双重免疫染色来研究健康和炎症性人牙周组织中的 sGC 的α-和β-亚基，并将这些发现与来自相同切片的破骨细胞进行比较。与健康牙周组织中的破牙骨质细胞相比，炎症条件下的破牙骨质细胞的 sGC 的α-和β-亚基的染色强度均降低，表明这些亚基的蛋白表达减少。因此，以非 NO 和血红素依赖性方式在炎症性牙周组织中激活 sGC 可以被认为是抑制牙骨质吸收的一种新的治疗策略。
