破骨細胞を介した変形性顎関節症の病態機構の解明

• Project/Area Number: 16791265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Kanazawa Medical University
• Principal Investigator: 金山 景錫 金沢医科大学, 医学部, 講師 (50329380)
• Project Period (FY): 2004 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 顎関節症 / 破骨細胞 / 破骨細胞分化促進因子 / 破骨細胞分化抑制因子 / 滑液 / 滑膜 / 変形性関節症 / joint effusion / MRI / サイトカイン / サイトカインレセプター / RANKL

Research Abstract

顎関節症で退行変性が生じる一因として破骨細胞の分化・成熟を抑制する破骨細胞形成抑制因子(Osteoprotegerin; OPG)が不足している可能性を報告したが(Oral Surg Oral Med Oral Pathol,2003)、今研究では促進因子である破骨細胞分化因子(receptor activator of NF-κB ligand; PANKL)の滑膜組織中での発現と退行変性との関連について調べた。対象・方法は手術適応の顎関節症IIIb型30関節・IV型20関節に対して全麻下で上関節腔の診断的鏡視により軟骨の退行変性、滑膜炎の程度を各10点法による定量的評価を行った。続いて滑膜組織を採取し、4%PFAで固定後、パラフィン切片を作製した。抗ヒトPANKL抗体を用いABC法による免疫染色を行い、組織中のPANKLの局在とその陽性率を算定し、鏡視所見と比較検討した。結果はPANKLの局在と平均陽性率は滑膜細胞で64%(2〜97)、血管内皮細胞で74%(8〜98)、線維芽細胞で63%(5〜97)であったが、いずれも鏡視所見(軟骨の退行変性:平均3(0〜10)、滑膜炎:平均5(2〜9))との間に相関を認めなかった。結論として滑膜組織におけるPANKLの発現は破骨細胞の分化・成熟の供給源となる可能性を示唆する一方で、退行変性はOPGの発現に左右されるのではないかと考えられた。またOPG/PANKLのみならず、顎関節滑液・滑膜に様々な化学伝達物質を検出し、これらが複雑に絡み合って病態を形成していることが判明した。

Research Products

• [Journal Article] Expression of receptor activator of nuclear factor-kB ligand (RANKL) in synovial tissue : Comparison with degradation of articular cartilage intemporomandibular joint disorders (2007)
  • Author(s): K Kaneyama, et al.
  • Journal Title: Oral Surgery, Oral Medicine, Oral Pathology (In press)
• [Journal Article] Prognostic factors in arthrocentesis of the temporomandibular joint : comparison of bradykinin, leukotriene B4, prostaglandin E2 and substance P level in synovial fluid between successful and unsuccessful cases (2007)
  • Author(s): K Kaneyama, et al.
  • Journal Title: Journal of Oral and Maxillofacial Surgery 65・2 Pages: 242-247
• [Journal Article] Anchored disk phenomenon with normally positioned disk of the temporomandibular joint : characteristics and behavior. (2007)
  • Author(s): K Kaneyama, et al.
  • Journal Title: Br J Oral Maxillofac Surg. (In press)
• [Journal Article] Specific expression of substance P in synovial tissues of patients with symptomatic, non-reducing internal derangement of the temporomandibular joint : Comparison with clinical findings. (2007)
  • Author(s): J Sato, K Kaneyama, et al.
  • Journal Title: Br J Oral Maxillofac Surg. (In press)
• [Journal Article] Electrophoretic separation of the synovial fluid proteins in patients with temporomandibular joint disorders. (2006)
  • Author(s): K Fujimura, K Kaneyama, et al.
  • Journal Title: Oral Surgery, Oral Medicine, Oral Pathology 101 Pages: 463-468
• [Journal Article] Analysis of tumor necrosis factor-alpha, interleukin-6, interleukin 1beta, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor, interleukin-1 soluble receptor type II, interleukin-1 receptor antagonist, and protein in the synovial fluid of patients with temporomandibular joint disorders. (2005)
  • Author(s): K Kaneyama, et al.
  • Journal Title: Oral Surg Oral Med Oral Pathol. 99 Pages: 276-284
• [Journal Article] Levels of soluble cytokine factors in temporomandibular joint effusions seen on magnetic resonance images. (2005)
  • Author(s): K Kaneyama, et al.
  • Journal Title: Oral Surg Oral Med Oral Pathol 99 Pages: 411-418
• [Journal Article] Vascular endothelial growth factor concentrations in synovial fluids of patients with symptomatic internal derangement of the temporomandibular joint. (2005)
  • Author(s): J Sato, K Kaneyama, et al.
  • Journal Title: J Oral Pathol Med 34 Pages: 170-177
• [Journal Article] Analysis of tumor necrosis factor-α, interleukin-6, interleukin-1β, soluble tumor necrosis factor receptors I and II, interleukin-6 soluble receptor (2005)
  • Author(s): K.Kaneyama, et al.
  • Journal Title: Oral Surg Oral Pathol Oral Radil Endod 99・3 Pages: 276-284
• [Journal Article] Levels of soluble cytokine factors in temporomandibular joint effusions see on magnetic resonance images. (2005)
  • Author(s): K.Kaneyama, et al.
  • Journal Title: Oral Surg Oral Pathol Oral Radil Endod 99・4 Pages: 411-418
• [Journal Article] Vascular Endothelial Growth Factor Concentrations in Synovial Fluids of Patients with Symptomatic Internal Derangement of the Temporomandibular Joint. (2005)
  • Author(s): J Sato, K.Kaneyama, et al.
  • Journal Title: J Oral Pathol & Med 34 Pages: 170-177