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

Tillgren, Viveka LU ; Ho, James C S; Önnerfjord, Patrik LU and Kalamajski, Sebastian LU (2015) In Journal of Biological Chemistry 290(2). p.918-925
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
290
issue
2
pages
918 - 925
publisher
ASBMB
external identifiers
  • pmid:25451920
  • wos:000347778200026
  • scopus:84920982810
ISSN
1083-351X
DOI
10.1074/jbc.M114.593541
language
English
LU publication?
yes
id
17c82df2-2ef8-476a-91e2-d5c02e80df73 (old id 4913259)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25451920?dopt=Abstract
date added to LUP
2015-01-08 15:57:11
date last changed
2017-10-22 03:31:08
@article{17c82df2-2ef8-476a-91e2-d5c02e80df73,
  abstract     = {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.},
  author       = {Tillgren, Viveka and Ho, James C S and Önnerfjord, Patrik and Kalamajski, Sebastian},
  issn         = {1083-351X},
  language     = {eng},
  number       = {2},
  pages        = {918--925},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Novel Small Leucine-Rich Protein Chondroadherin-like (CHADL) is Expressed in Cartilage and Modulates Chondrocyte Differentiation.},
  url          = {http://dx.doi.org/10.1074/jbc.M114.593541},
  volume       = {290},
  year         = {2015},
}