title: Extracellular acidosis accelerates bone resorption by enhancing osteoclast survival, adhesion, and migration.
abstract: Acidic extracellular pH promotes osteoporotic bone loss by osteoclast activation. However, the change of osteoclastic cell behavior in acidosis-stimulated bone resorption process is unknown. We found that lowering extracellular pH induced an increase in the survival, adhesion, and migration of mature osteoclasts with a full actin ring, leading to enhanced pit formation on dentine slices. Acidosis upregulated osteopontin, which is an Arg-Gly-Asp (RGD) motif-containing matrix protein secreted from osteoclasts and acts as a common modulator for their survival, adhesion, and migration. A synthetic RGD peptide treatment blocked acidosis-induced osteoclast adhesion and migration, likely by competing with the RGD motif-containing extracellular matrix proteins for cell surface integrin binding. We finally observed that acidosis was associated with activation of osteoclast survival/adhesion/migration-related Pyk2, Cbl-b, and Src signals. Collectively, the findings indicate that extracellular acidosis stimulates bone resorption by extending osteoclast survival and facilitating osteoclast adhesion and migration.
authors.affiliation: Department of Microbiology, Aging-associated Vascular Disease Research Center, Yeungnam University College of Medicine, Daegu 705-717, Republic of Korea.
authors.forename: Heejin
authors.initials: H
authors.lastname: Ahn
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Lee
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.forename: Daewon
authors.initials: D
authors.lastname: Jeong
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology*; D002448:Cell Adhesion; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C118387:Cblb protein, mouse; D016326:Extracellular Matrix Proteins; D050721:Proto-Oncogene Proteins c-cbl; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases