Localization and Functions of Integrins and Proteinase in Osteoclasts

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06671827
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Morphological basic dentistry
• Research Institution: Showa University
• Principal Investigator: SASAKI Takahisa Showa University, Oral Anatomy, Associate Professor, 歯学部, 助教授 (50129839)
• Co-Investigator(Kenkyū-buntansha): KUROIWA Mie Showa University, Oral Anatomy, Assistant Professor, 歯学部, 講師 (90153395) ; TACHIKAWA Tetsuhiko Showa University, Pathology, Associate Professor, 歯学部, 助教授 (10085772) ; SUDA Tatsuo SHowa University, Biochemistry, Professor, 歯学部, 教授 (90014034)
• Project Period (FY): 1994 – 1995
• Keywords: Osteoclast / Integrin / RGD peptide / Cathepsin / E-64 / Ultrastructure / in vitro / in vivo

Research Abstract

In the present study, we examined the subcellular localization and function of the alphaVB3 integrin in primary rat osteoclasts and mouse osteoclast-like multinucleated cells (OCLs) formed in vitro. At the ultrastructural level, the specific immunoreactivity of both alphaV and B3 subunits was localized not only along the plasma membranes of osteoclast ruffled borders and basolateral membranes but also in clear zones. Addition of GRGDS (Gly-Arg-Gly-Asp-Ser) peptide to the culture medium during a pit formation assay reduced resorbed areas on dentine slices.
The treatment with GRGDS peptide also inhibited the formation of a ringed structure of F-actin (an "actin ring") in OCLs on dentine slices. Electron microscopic analysis revealed that OCLs treated with GRGDS peptide could adhere to dentine slices with unusually broad or poorly defined clear zones but did not form the ruffled border structure. These results suggest that integrin alphaVB3 subunits localized in the ruffled border-clear zone complex of osteoclasts are essential molecules for the functional osteoclast-to-bone matrix interaction and the structural polarization of osteoclasts.

Research Products

• [Publications] Sasaki T.: "Recent Advances in the Ultrastructural Assessment of Osteoclastic Resorptive Functions" Microscopy Research and Technique. 33. 182-191 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Debari K.,Sasaki T.,Udagawa N.,Rifkin B.R.: "An Ultrastructural Evaluation of the Effects of Cysteine-Proteinase Inhibitors of Osteoclastic Resorptive Functions" Calcified Tissue International. 56. 566-570 (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki T.,Udagawa N.,Hong M.H.,Debar K.: "Osteoclastic Bone Resorbing Function : Cell-Motrix In teractions During Demineralization and Degradation of Bone Matrix" The Biological Mechanisms of Tooth Eruption,Resorption and Replacement by Implants. 107-114 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki, T.: "Recent Advances in the Ultrastructural Assessment of Osteoclastic Resorptive Functions" Microscopy Research and Technique. 33. 182-191 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Debari, K., Sasaki, T., Udagawa, N., Rifkin, B.R.: "An Ultrastructural Evaluation of the Effects of Cysteine-Proteinase Inhibitors on Osteoclastic Resorptive Functions" Calcified Tissue International. 56. 566-570 (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki, T., Udagawa, N., Hong, M.H., Debari, K.: The Biological Mechanisms of Tooth Eruption, Resorption and Replacement by Implants (Ed : Davidovitch, z.) (Osteoclastic Bone Resorbing Function : Cell-Matrix Interactions During Demineralization and Degradation of Bone Matrix). Boston, EBSCO Media, 107-114 (1994)
  • Description: 「研究成果報告書概要(欧文)」より