title: Age-related bone deterioration is diminished by disrupted collagen sensing in integrin α2β1 deficient mice.
abstract: Collagen binding integrins are of essential importance in the crosstalk between cells and the extracellular matrix. Integrin α2β1 is a major receptor for collagen I, the most abundant protein in bone. In this study we show for the first time that integrin α2 deficiency is linked to collagen type I expression in bone. Investigating the femurs of wild type and integrin α2β1 deficient mice, we found that loss of integrin α2 results in altered bone properties. Histomorphometric analysis of integrin α2 long bones displayed more trabecular network compared to wild type bones. During age related bone loss the integrin α2β1 deficient bones retain trabecular structure even at old age. These findings were supported by functional, biomechanical testing, wherein the bones of integrin α2β1 deficient mice do not undergo age-related alteration of biomechanical properties. These results might be explained by the increased presence of collagen in integrin α2β1 deficient bone. Collagen type I could be detected in higher quantities in the integrin α2β1 deficient bones, forming abnormal, amorphous fibrils. This was linked to higher expression levels of collagen type I and other bone formation related proteins as alkaline phosphatase of integrin α2β1 deficient osteoblasts. Osteoclasts of integrin α2β1 deficient mice did not show any differences. Consequently these results indicate that the absence of integrin α2β1 alleviates the effects of age related bone degradation through over-expression of collagen type I and demonstrate a molecular mechanism how collagen binding integrins might directly impact bone aging.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Muenster, Germany. Richard.Stange@ukmuenster.de
authors.forename: Richard
authors.initials: R
authors.lastname: Stange
authors.forename: Daniel
authors.initials: D
authors.lastname: Kronenberg
authors.forename: Melanie
authors.initials: M
authors.lastname: Timmen
authors.forename: Jens
authors.initials: J
authors.lastname: Everding
authors.forename: Heriburg
authors.initials: H
authors.lastname: Hidding
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
authors.forename: Michael
authors.initials: M
authors.lastname: Holtkamp
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raschke
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001696:Biomechanical Phenomena; D001862:Bone Resorption / Q000235:genetics / Q000473:pathology*; D002113:Calcification, Physiologic / Q000235:genetics; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D004210:Dissection; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D024022:Fibrillar Collagens / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D038982:Integrin alpha2beta1 / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024022:Fibrillar Collagens; D038982:Integrin alpha2beta1; D012333:RNA, Messenger
keywords: Aging; Bone metabolism; Collagen type I; Collagen-binding integrins; Osteoporosis