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

来源于牙龈和牙周韧带的成纤维细胞表现成骨诱导特性；人牙周韧带细胞破骨细胞分化和寿命的调控（Kobayashi）和破骨生成抑制因子（OCIF）的表达（Kurihara）。小鼠克隆牙周韧带细胞表达骨相关细胞外基质蛋白如1型胶原、骨钙素（OCN）和骨桥蛋白（OPN） （Murakami）脂多糖（LPS）是牙周病的重要致病因子。LPS降低了大鼠颅细胞和与精神应激相关的P物质的骨结节形成，增强了LPS的抑制作用，提示LPS和P物质影响牙周骨分化（Nagata）。lps诱导的TNF-α因子（LITAF）是一种新的单核细胞转录因子，对LITAF启动子的分析表明，LITAF启动子中有一个位于-7 ~ -43核苷酸范围内的34 bp序列域，该序列域对LITAF基因转录的上调起作用（Myoukai）。降钙素基因相关肽（CGRP）受体在未成熟成骨人MG63细胞中的表达（Okuda）。LPS通过toll样受体4促进破骨细胞的存活，但破骨细胞在LPS作用下产生的细胞因子与巨噬细胞不同（Nishihara）。此外，放线菌胞囊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围病变的破坏性介质和激活新骨形成中发挥重要作用（Maeda）。rhBMP-2与屏障膜的结合具有通过直接在膜的内表面诱导成骨细胞来产生和维持骨的预期形状的优势（Irie）。BMP-4, -5， -6对培养牙周韧带细胞DNA合成和骨相关蛋白表达的影响（Kurihara）。骨唾液蛋白（BSP）样分子与整合素αvβ3 （Maeno）相互作用介导人牙周膜细胞与牙釉质基质源性蛋白的附着。龈沟液中1型前胶原前肽（P1CP）是牙周炎患者骨转换的有用标志物。低水平激光照射（low- low laser辐照，LLLI）对骨形成的刺激作用被评估，LLLI增加骨甘素基因的表达与基质蛋白和生长因子的骨形成有关（Abiko）。x线观察显示，重度破坏性牙周炎（Yaegashi）术后10年经皮瓣治疗的牙槽骨均恢复正常。环氧化酶-2 （COX-2）抑制剂不仅抑制炎症性骨吸收因子的产生，而且增加OCIF （Kurihara）的产生。基质金属蛋白酶（MMP）抑制仓鼠实验性牙周炎的牙槽骨吸收。局部使用双膦酸盐也能抑制大鼠和狗的牙槽骨吸收（Shibutani）。虽然他汀类药物没有增加人牙周韧带细胞碱性磷酸酶活性，但他汀类药物可降低人牙龈成纤维细胞培养基中IL-6的含量，提示他汀类药物具有抗炎和成骨作用（Yamamoto Less）

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