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Sebastian Kalamajski

Assistant researcher

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Novel Small Leucine-Rich Protein Chondroadherin-like (CHADL) is Expressed in Cartilage and Modulates Chondrocyte Differentiation.

Author

  • Viveka Tillgren
  • James C S Ho
  • Patrik Önnerfjord
  • Sebastian Kalamajski

Summary, in English

The constitution and biophysical properties of extracellular matrices can dramatically influence cellular phenotype during development, homeostasis, or pathogenesis. These effects can be signaled through a differentially regulated assembly of collagen fibrils, orchestrated by a family of collagen-associated Small Leucine-Rich Proteins, SLRPs. In this report, we describe the tissue-specific expression and function of a previously uncharacterized SLRP Chondroadherin-like (CHADL). We have developed antibodies against CHADL and, by immunohistochemistry, detected CHADL expression mainly in skeletal tissues, particularly in fetal cartilage and in pericellular space of adult chondrocytes. In situ hybridizations and immunoblots on tissue lysates confirmed this tissue-specific expression pattern. Recombinant CHADL bound collagen in cell culture, and inhibited in vitro collagen fibrillogenesis. After Chadl shRNA knockdown chondrogenic ATDC5 cells increased their proliferation and differentiation, indicated by increased transcript levels of Sox9, Ihh, Col2a1, and Col10a1. The knockdown increased collagen II and aggrecan deposition in the cell layers. Microarray analysis of the knockdown samples suggested collagen receptor-related changes, although other upstream effects could not be excluded. Together, our data indicate that the novel SLRP CHADL is expressed in cartilaginous tissues, influences collagen fibrillogenesis, and modulates chondrocyte proliferation and differentiation. CHADL appears to have a negative regulatory role, possibly ensuring the formation of a stable extracellular matrix.

Department/s

  • Rheumatology
  • Åke Oldberg´s group

Publishing year

2015

Language

English

Pages

918-925

Publication/Series

Journal of Biological Chemistry

Volume

290

Issue

2

Document type

Journal article

Publisher

ASBMB

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Åke Oldberg´s group

ISBN/ISSN/Other

  • ISSN: 1083-351X