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.
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Authors | B Dabovic, R Levasseur, L Zambuto, Y Chen, G Karsenty, D B Rifkin |
Journal | Bone
(Bone)
Vol. 37
Issue 1
Pg. 25-31
(Jul 2005)
ISSN: 8756-3282 [Print] United States |
PMID | 15878314
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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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
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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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