Study on pathogenesis and treatment of periodontal disease which is focused in bone metabolism

来自牙龈和牙周韧带的成纤维细胞显示出骨诱导特性;破骨细胞分化和生命周期的调节（小林）和人牙周韧带细胞（栗原）中破骨细胞生成抑制因子（OCIF）的表达。实验还发现，小鼠牙周膜细胞克隆表达骨相关的细胞外基质蛋白，如1型胶原、骨钙素（OCN）和骨桥蛋白（OPN）（Murakami）。脂多糖（LPS）是牙周病的一种潜在致病因子。LPS降低大鼠颅骨细胞中的骨结节形成，与精神应激相关的P物质增强LPS的抑制作用，表明LPS和P物质影响牙周骨分化（Nagata）。LPS诱导的TNF-α因子（LITAF）是人单核细胞中一种新的转录因子，LITAF启动子序列分析表明，LITAF启动子区位于LITAF启动子区的-7 ...更多信息 6至-43的序列结构域，并且该新序列结构域有助于LITAF基因转录的上调（Myoukai）。降钙素基因相关肽（CGRP）受体在未成熟的人成骨细胞MG 63细胞（Okuda）中表达。LPS通过Toll样受体4促进破骨细胞的存活，但破骨细胞响应LPS的细胞因子产生与巨噬细胞不同（Nishihara）。此外，伴放线放线菌的荚膜多糖抑制人牙龈成纤维细胞中IL-6和IL-8的产生（Nishihara）巨噬细胞参与根尖牙周炎的进展和消退，表达TGF-β1的巨噬细胞可能在减少根尖周病变中的破坏性介质和激活新骨形成（Maeda）中起重要作用。rhBMP-2和屏障膜的组合通过直接在膜的内表面上诱导成骨细胞（Irie）而在产生和维持骨的预期形状方面具有优势。BMP-4、BMP-5、BMP-6对牙周膜细胞DNA合成及骨相关蛋白表达的影响。人牙周膜细胞与釉基质衍生蛋白的附着是通过骨唾液酸蛋白（BSP）样分子和整合素αvβ3（Maeno）之间的相互作用介导的。龈沟液中的1型前胶原前肽（P1 CP）是牙周炎患者骨转换的有用指标（Nagata）。评价了低强度激光照射（LLLI）对骨形成的刺激作用，LLLI引起的骨甘氨酸基因表达增加与骨形成相关，并与基质蛋白和生长因子（Abiko）相关。放射学观察显示，重度破坏性牙周炎（八重）患者经翻瓣术治疗10年后牙槽骨恢复正常。环氧化酶-2（考克斯-2）抑制剂不仅能抑制炎性骨吸收因子的产生，而且能增加OCIF（栗原）的产生。基质金属蛋白酶（MMP）管理抑制牙槽骨吸收仓鼠的实验性牙周炎（Nagata）。局部给予双膦酸盐也可抑制大鼠和犬的牙槽骨吸收（Shibutani）。虽然他汀类药物没有增加人牙周膜细胞中的碱性磷酸酶活性，但他汀类药物减少了人牙龈成纤维细胞培养基中的IL-6的量，这表明他汀类药物具有抗炎作用以及骨形成作用（Yamamoto）。

Fibroblasts derived from gingiva and periodontal ligaments showed osteoinductive properties ; regulation of osteoclast differentiation and life period (Kobayashi) and expression of osteoclastgenesis inhibitory factor (OCIF) in human periodontal ligament cells (Kurihara). It was also found that mouse clonal periodontal ligament cells expressed bone-related extracellular matrix proteins such as type-1 collagen, osteocalcin (OCN) and osteopontin (OPN) (Murakami)Lipopolysaccharide (LPS) is a potent pathogenic factor in periodontal diseases. LPS decreased bone nodule formation in rat calvaria cells and substance P, which is associated with mental stress, augumented the inhibitory action of LPS, suggesting that LPS and substance P influence in periodontal bone differentiation (Nagata). LPS-induced TNF-α factor (LITAF) was identified as a novel transcription factor in human monocytic cells and characterization of LITAF promoter revealed that a 34-bp sequence domain located from nucleotides -7 … More 6 to -43 in the promoter and this new sequence domain contributed the up-regulation of LITAF gene transcription (Myoukai). The receptors of calcitonin gene-related peptide (CGRP) expressed in immature osteoblastic human MG63 cells (Okuda). LPS promoted the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to LPS is different from that of macrophages (Nishihara). Also, capsular polysaccharide from A.actinomycetemcomitans inhibited IL-6 and IL-8 production in human gingival fibroblasts (Nishihara)Macrophages are involved in both progression and resolution of apical periodontitis, and macrophages expressing TGF-β1 may play an important role in reducing the destructive mediators in periapical lesions and in the activation of new bone formation (Maeda). The combination of rhBMP-2 and barrier membrane had advantagees in producing and maintaining bone in the intended shape by inducing osteoblasts directly on the inner surface of the membrane (Irie). BMP-4, -5, -6 affected on DNA synthesis and expression of bone-related proteins in cultured periodontal ligament cells (Kurihara). Attachment of human periodontal ligament cells to enamel matrix-derived protein was mediated via interaction between bone sialoprotein (BSP)-like molecules and integrin αvβ3 (Maeno). Propeptide of type-1 procollagen (P1CP) in gingival crevicular fluid was a useful marker for bone turnover in periodontitis (Nagata). Stimulatory effect of low-level laser irradiation (LLLI) on bone formation was evaluated and the increased expression of osteoglycin gene by LLLI was associated with bone formation in concert with matrix proteins and growth factors (Abiko). Radiographic observation revealed that alveolar bone treated with flap operation was recovered after 10 years in severe destructive periodontitis (Yaegashi)Cycloxygenase-2 (COX-2) inhibitor not only inhibited the production of inflammatory bone-resorptive factors but also increased the production of OCIF (Kurihara). Matrix metaloprotease (MMP) administration inhibited alveolar bone resorption in hamster's experimental periodontitis (Nagata). Local administration of bisphosphonate also inhibited alveolar bone resorption in rats and dogs (Shibutani). Although statin did not increase alkaline phosphatase activity in human periodontal ligament cells, amount of IL-6 in culture medium of human gingival fibroblasts was decreased by statin, suggesting that statin has anti-inflammatory action as well as bone-forming action (Yamamoto) Less