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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.
AuthorsB Dabovic, R Levasseur, L Zambuto, Y Chen, G Karsenty, D B Rifkin
JournalBone (Bone) Vol. 37 Issue 1 Pg. 25-31 (Jul 2005) ISSN: 8756-3282 [Print] United States
PMID15878314 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Amino Acids
  • Collagen Type I
  • Collagen Type X
  • Latent TGF-beta Binding Proteins
  • Ltbp1 protein, mouse
  • Ltbp3 protein, mouse
  • RNA
  • deoxypyridinoline
Topics
  • Adaptor Proteins, Signal Transducing (deficiency, genetics)
  • Age Factors
  • Amino Acids (urine)
  • Animals
  • Animals, Newborn
  • Cartilage (pathology)
  • Cell Count
  • Chondrocytes (metabolism, pathology)
  • Collagen Type I (analysis)
  • Collagen Type X (analysis)
  • Femur (chemistry, pathology)
  • Gene Expression (genetics)
  • Humerus (pathology)
  • Immunohistochemistry
  • Latent TGF-beta Binding Proteins
  • Mice
  • Mice, Knockout
  • Osteoblasts (metabolism, pathology)
  • Osteoclasts (metabolism)
  • Osteogenesis (physiology)
  • Osteopetrosis (genetics, metabolism, pathology)
  • Phenotype
  • RNA (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spine (pathology)

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