The elucidation of the role of lipid in bone resorption of inflammatory bone diseases; in particular, the exploration of the role of LOX-1 as an oxidized LDL receptor

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293376
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Meikai University
• Principal Investigator: HAKEDA Yoshiyuki 明海大学, 歯学部, 教授 (90164772)
• Co-Investigator(Kenkyū-buntansha): SATO Takuya 明海大学, 歯学部, 講師 (00316689) ; OKAYASU Mari 東京大学, 医学部付属病院, 特任臨床医 (10610941) ; OGASAWARA Toru 東京大学, 医学部付属病院, 講師 (20359623) ; SAWAMURA Tatsuya 信州大学, 医学部, 教授 (30243033) ; ITO Junta 明海大学, 歯学部, 助教 (40609096) ; HAYASHIDA Chiyomi 明海大学, 歯学部, 助教 (40710900) ; KANEDA Toshio 星薬科大学, 薬学部, 講師 (70339521)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 炎症性骨破壊 / 破骨細胞 / 骨芽細胞 / LOX-1

Outline of Final Research Achievements

Lectin-like oxidized LDL receptor-1 (LOX-1) was downregulated with osteoclast (OC) differentiation. LOX-1 negatively regulates OC differentiation by suppressing the cell-cell fusion of preOC. The LOX-1-deleted (LOX-1-/-) mice consistently decreased the trabecular bone mass because of elevated bone resorption. In contrast, when the calvaria was inflamed by LPS-injection, the inflammation-induced bone destruction was reduced by LOX-1 deficiency. The expression of RANKL, a trigger molecule for OC differentiation, evoked by the inflammation was abrogated in the LOX-1-/- mice. Osteoblasts (OBs), the major RANKL producers, expressed LOX-1 in response to IL-1β and PGE2. In the co-culture of LOX-1-/- OBs and wild-type OC precursors, the osteoclastogenesis induced by IL-1β and PGE2 decreased in parallel with the downregulation of RANKL expression in OBs. Thus, LOX-1 abrogation results in resistance to inflammatory bone destruction, despite promoting osteoclastogenesis in the steady state.

Free Research Field

口腔解剖学