title: Osteopetrosis-like phenotype in latent TGF-beta binding protein 3 deficient mice.
abstract: LTBPs are extracellular matrix proteins resembling fibrillins. LTBP-1, 3, and 4 covalently bind latent TGF-beta and modulate tissue levels of this potent cytokine through regulation of its secretion, localization, and/or activation. To address LTBP function in vivo, we generated Ltbp-3 null mice. Ltbp-3-/- animals developed craniofacial abnormalities due to early ossification of the skull base synchondroses and displayed reduced body size. In addition, histological examination of Ltbp-3-/- skeletons revealed an increase in bone mass. The osteoblast numbers and mineral apposition rates were decreased in Ltbp-3-/- mice, whereas the osteoclast numbers were similar in null and wild type mice. Histological examination revealed persistence of cartilage remnants in Ltbp-3-/- trabecular bone. Taken together, these results indicate that the Ltbp-3-/- high bone mass phenotype was due to a defect in bone resorption. We hypothesize that lack of Ltbp-3 results in decreased levels of TGF-beta in bone and cartilage, which leads to compromised osteoclast function and decreased bone turnover.
authors.affiliation: Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dabovic
authors.forename: R
authors.initials: R
authors.lastname: Levasseur
authors.forename: L
authors.initials: L
authors.lastname: Zambuto
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Karsenty
authors.forename: D B
authors.initials: DB
authors.lastname: Rifkin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D000367:Age Factors; D000596:Amino Acids / Q000652:urine; D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000473:pathology; D002452:Cell Count; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000032:analysis; D024121:Collagen Type X / Q000032:analysis; D005269:Femur / Q000737:chemistry / Q000473:pathology; D015870:Gene Expression / Q000235:genetics; D006811:Humerus / Q000473:pathology; D007150:Immunohistochemistry; D053779:Latent TGF-beta Binding Proteins; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D010022:Osteopetrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013131:Spine / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D024042:Collagen Type I; D024121:Collagen Type X; D053779:Latent TGF-beta Binding Proteins; C509033:Ltbp1 protein, mouse; C509039:Ltbp3 protein, mouse; D012313:RNA; C036020:deoxypyridinoline