title: Effects of altered bone remodeling and retention of cement lines on bone quality in osteopetrotic aged c-Src-deficient mice.
abstract: Cement lines represent mineralized, extracellular matrix interfacial boundaries at which bone resorption by osteoclasts is followed by bone deposition by osteoblasts. To determine the contribution of cement lines to bone quality, the osteopetrotic c-Src mouse model-where cement lines accumulate and persist as a result of defective osteoclastic resorption-was used to investigate age-related changes in structural and mechanical properties of bone having long-lasting cement lines. Cement lines of osteopetrotic bones in c-Src knockout mice progressively mineralized with age up to the level that the entire matrix of cement lines was lost by EDTA decalcification. While it was anticipated that suppressed and abnormal remodeling, together with the accumulation of cement line interfaces, would lead to defective bone quality with advancing age of the mutant mice, unexpectedly, three-point bending tests of the long bones of 1-year-old c-Src-deficient mice indicated significantly elevated strength relative to age-matched wild-type bones despite the presence of numerous de novo microcracks. Among these microcracks in the c-Src bones, there was no sign of preferential propagation or arrest of microcracks along the cement lines in either fractured or nonfractured bones of old c-Src mice. These data indicate that cement lines are not the site of a potential internal failure of bone strength in aged c-Src osteopetrotic mice and that abundant and long-lasting cement lines in these osteopetrotic bones appear to have no negative impacts on the mechanical properties of this low-turnover bone despite their progressive hypermineralization (and thus potential brittleness) with age.
authors.affiliation: Department of Hard Tissue Engineering, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takakuda
authors.forename: Hiroko N
authors.initials: HN
authors.lastname: Matsumoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyata
authors.forename: Otto
authors.initials: O
authors.lastname: Baba
authors.forename: Makoto J
authors.initials: MJ
authors.lastname: Tabata
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ushiki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oda
authors.forename: Marc D
authors.initials: MD
authors.lastname: McKee
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016723:Bone Remodeling / Q000235:genetics*; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000081247:CSK Tyrosine-Protein Kinase; D002113:Calcification, Physiologic / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D050723:Fractures, Bone / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013718:Tensile Strength / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology; D019061:src-Family Kinases
chemical_list: D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases