Chondromodulin I Is Dispensable during Enchondral Ossification and Eye Development

Brandau, Oliver; Aszódi, Attila; Hunziker, Ernst B.; Neame, Peter J.; Vestweber, Dietmar; Fässler, Reinhard

doi:10.1128/mcb.22.18.6627-6635.2002

Cited by 23 publications

(17 citation statements)

References 34 publications

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“…This postnatal proliferation deficit probably caused reduced cell density in P14 and adult tendons, since no apoptotic loss of cells was observed. Interestingly, the C-terminal domain of ChM-I induced proliferation of chondrocytes in vitro (27), but mice lacking ChM-I had no alterations in skeletal development or chondrocyte proliferation (11,32). Despite the lower cell numbers, Tnmd-deficient tendons had the same size as wild-type tendons, suggesting that either the remaining tenocytes were able to compensate the loss of cells or that the turnover of ECM is delayed in Tnmd-deficient tendons.…”

Section: Discussionmentioning

confidence: 96%

“…OIR was induced at postnatal day 7 (P7) in wild-type, Tnmd-null, ChM-I-null (11), and Tnmd/ChM-I double-null mice. For 5 days the mice were kept with a lactating female in a ventilation-controlled cage in 75% Ϯ 3% oxygen.…”

Section: Methodsmentioning

confidence: 99%

“…However, deletion of ChM-I in mice did not affect endothelial or chondrocyte proliferation. Since the Tnmd gene was not upregulated in ChM-I-deficient tissue, the lack of ChM-I is likely to be compensated by other factors (11).…”

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confidence: 99%

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Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

Docheva

Hunziker

Fässler

et al. 2005

Molecular and Cellular Biology

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382

376

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Tenomodulin (Tnmd) is a member of a new family of type II transmembrane glycoproteins. It is predominantly expressed in tendons, ligaments, and eyes, whereas the only other family member, chondromodulin I (ChM-I), is highly expressed in cartilage and at lower levels in the eye and thymus. The C-terminal extracellular domains of both proteins were shown to modulate endothelial-cell proliferation and tube formation in vitro and in vivo. We analyzed Tnmd function in vivo and provide evidence that Tnmd is processed in vivo and that the proteolytically cleaved C-terminal domain can be found in tendon extracts. Loss of Tnmd expression in gene targeted mice abated tenocyte proliferation and led to a reduced tenocyte density. The deposited amounts of extracellular matrix proteins, including collagen types I, II, III, and VI and decorin, lumican, aggrecan, and matrilin-2, were not affected, but the calibers of collagen fibrils varied significantly and exhibited increased maximal diameters. Tnmd-deficient mice did not have changes in tendon vessel density, and mice lacking both Tnmd and ChM-I had normal retinal vascularization and neovascularization after oxygeninduced retinopathy. These results suggest that Tnmd is a regulator of tenocyte proliferation and is involved in collagen fibril maturation but do not confirm an in vivo involvement of Tnmd in angiogenesis.Tendons and ligaments connect the elements of the musculoskeletal system and are composed of a densely packed collagen-rich connective tissue able to withstand high tensile forces. Collagen type I is predominant, but collagen types III,

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Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

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Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

Docheva

Hunziker

Fässler

et al. 2005

Molecular and Cellular Biology

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382

376

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“…Nonradioactive in situ hybridization on tissue sections for mouse collagen II (Col2a1), collagen X (Col10a1), Indian hedgehog (Ihh), and Parathyroid hormone/Parathyroid hormone-related peptide receptor (Ppr) mRNA was performed as described by Brandau et al (5). Briefly, newborn limbs were fixed in 4% PFA in Tris-buffered saline (TBS) (pH 9.5) and subsequently dehydrated and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

Matrilin-3 Is Dispensable for Mouse Skeletal Growth and Development

Kobbe

Nicolae

et al. 2004

Molecular and Cellular Biology

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Matrilin-3 belongs to the matrilin family of extracellular matrix (ECM) proteins and is primarily expressed in cartilage. Mutations in the gene encoding human matrilin-3 (MATN-3) lead to autosomal dominant skeletal disorders, such as multiple epiphyseal dysplasia (MED), which is characterized by short stature and earlyonset osteoarthritis, and bilateral hereditary microepiphyseal dysplasia, a variant form of MED characterized by pain in the hip and knee joints. To assess the function of matrilin-3 during skeletal development, we have generated Matn-3 null mice. Homozygous mutant mice appear normal, are fertile, and show no obvious skeletal malformations. Histological and ultrastructural analyses reveal endochondral bone formation indistinguishable from that of wild-type animals. Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family. Altogether, our findings suggest functional redundancy among matrilins and demonstrate that the phenotypes of MED disorders are not caused by the absence of matrilin-3 in cartilage ECM.

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“…Nonradioactive in situ hybridization on tissue sections for Col2a1, Col10a1, Ihh, and PTH/PTHrP receptor (Ppr) was performed as described by Brandau et al (2002). Radioactive in situ hybridization was performed as described (Aszodi et.…”

Section: Skeletal Analysesmentioning

confidence: 99%

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

Aszódi¹,

Hunziker²,

Brakebusch³

et al. 2003

Genes Dev.

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292

275

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␤1 integrins are highly expressed on chondrocytes, where they mediate adhesion to cartilage matrix proteins. To assess the functions of ␤1 integrin during skeletogenesis, we inactivated the ␤1 integrin gene in chondrocytes. We show here that these mutant mice develop a chondrodysplasia of various severity. ␤1-deficient chondrocytes had an abnormal shape and failed to arrange into columns in the growth plate. This is caused by a lack of motility, which is in turn caused by a loss of adhesion to collagen type II, reduced binding to and impaired spreading on fibronectin, and an abnormal F-actin organization. In addition, mutant chondrocytes show decreased proliferation caused by a defect in G1/S transition and cytokinesis. The G1/S defect is, at least partially, caused by overexpression of Fgfr3, nuclear translocation of Stat1/Stat5a, and up-regulation of the cell cycle inhibitors p16 and p21. Altogether these findings establish that ␤1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur.[Keywords: Integrin; fibronectin; endochondral ossification; growth plate; cytokinesis; FGF] Supplemental material is available at http://www.genesdev.org.

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Chondromodulin I Is Dispensable during Enchondral Ossification and Eye Development

Cited by 23 publications

References 34 publications

Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

Tenomodulin Is Necessary for Tenocyte Proliferation and Tendon Maturation

Matrilin-3 Is Dispensable for Mouse Skeletal Growth and Development

β1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis

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