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:
https://lup.lub.lu.se/record/4913259
- author
- Tillgren, Viveka
LU
; Ho, James C S
; Önnerfjord, Patrik
LU
and Kalamajski, Sebastian
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 290
- issue
- 2
- pages
- 918 - 925
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:25451920
- wos:000347778200026
- scopus:84920982810
- pmid:25451920
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M114.593541
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Åke Oldberg´s group (013212049), Connective Tissue Biology (013230151)
- 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
- 2016-04-01 11:12:36
- date last changed
- 2022-04-05 00:55:56
@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 = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Novel Small Leucine-Rich Protein Chondroadherin-like (CHADL) is Expressed in Cartilage and Modulates Chondrocyte Differentiation.}},
url = {{https://lup.lub.lu.se/search/files/2470605/7697074.pdf}},
doi = {{10.1074/jbc.M114.593541}},
volume = {{290}},
year = {{2015}},
}