title: The novel small leucine-rich protein chondroadherin-like (CHADL) is expressed in cartilage and modulates chondrocyte differentiation.
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 developed antibodies against CHADL and, by immunohistochemistry, detected CHADL expression mainly in skeletal tissues, particularly in fetal cartilage and in the 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 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 differentiation. CHADL appears to have a negative regulatory role, possibly ensuring the formation of a stable extracellular matrix.
authors.affiliation: From the Departments of Clinical Sciences and.
authors.forename: Viveka
authors.initials: V
authors.lastname: Tillgren
authors.affiliation: Experimental Medical Sciences, Lund University, 22184 Lund, Sweden.
authors.forename: James C S
authors.initials: JC
authors.lastname: Ho
authors.affiliation: From the Departments of Clinical Sciences and.
authors.forename: Patrik
authors.initials: P
authors.lastname: Önnerfjord
authors.affiliation: From the Departments of Clinical Sciences and Sebastian.Kalamajski@med.lu.se.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kalamajski
mesh_terms: D002356:Cartilage / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D024043:Collagen Type II / Q000096:biosynthesis; D005109:Extracellular Matrix; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000096:biosynthesis; D006801:Humans; D055758:SOX9 Transcription Factor / Q000096:biosynthesis
chemical_list: C000596977:CHADL protein, human; C499177:COL2A1 protein, human; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D053823:Hedgehog Proteins; C509246:IHH protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human
keywords: Cartilage; Chondrocyte; Chondrogenesis; Collagen; Connective Tissue