title: The osteoclasts attach to the bone surface where the extracellular calcium concentration decreases.
abstract: Osteoclasts demineralize and resorb bone once they attach to its surface. However, it's still unclear how the osteoclasts choose the specific sites for their attachments. It is postulated in this article that the decreased extracellular free ionized calcium concentration (Ca2+[e]) can provide a microenvironment for osteoclasts to recognize and then initiate the attachment process. The osteoclasts initially attach to the bone surface via integrating its integrin αvβ3and RGD containing ligands in bone matrix. Through the interaction with RGD-containing ligand, the integrin αvβ3forms carboxylate oxygen noncovalent, which is further stabilized by accompanied electrostatic interaction between the Ca2+and the β3subunit. There are two types of cation-binding sites on the β3subunit: the high affinity Ca2+binding site ("LC" site) that activates the osteoclasts by promoting the combination; the low affinity Ca2+binding site ("I" site, also named ADMIDAS) that deactivates the osteoclasts by dissociating the combination and it can override the "LC" site's positive effect on osteoclasts when necessary. Normally the Ca2+concentration of bone extracellular fluid is maintained within a normal range by osteocytes, keeping the "I" sites activated. When the osteocytes' function stalls and the ambient Ca2+concentration falls below the affinity discrimination threshold between the "I" site and the "LC" site, the "LC" site's promoting function starts to out compete the "I" site in its inhibitory effect, in which case the inactive integrin αvβ3turns into an extended active form and the osteoclasts start to attach, signifying the initiation of bone resorption.
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Bilu
authors.initials: B
authors.lastname: Xiang
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Gan
authors.affiliation: The State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Chengdu, China. yhyang6812@scu.edu.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
mesh_terms: D001665:Binding Sites; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008962:Models, Theoretical; D009842:Oligopeptides / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D039302:Integrin alphaVbeta3; D008024:Ligands; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium
keywords: Bone resorption; Ca2+ Concentration; Cell attachment; Integrin; αvβ3