title: Collagen II regulates chondroycte integrin expression profile and differentiation.
abstract: Collagen II is the major fibril-forming collagen in cartilage. Complete absence of collagen II in mice is not compatible with life and in humans mutations in the COL2A1 gene lead to osteochondrodysplasias with diverse phenotypes. However, mechanistic studies on how chondrocytes respond to a lack of collagen II in their extracellular matrix are limited. Primary mouse chondrocytes were isolated from knee joints of newborn mice and transfected with siRNA targeting Col2α1 to suppress collagen II expression. The expression of integrin receptors and matrix proteins was investigated by RT-PCR and immunoblots. The localization of matrix components was evaluated by immunostaining. Signaling pathways and the differentiation state of chondrocytes was monitored by RT-PCR and flow cytometry. We demonstrate that in the absence of collagen II chondrocytes start to produce collagen I. Some binding partners of collagen II are partially lost from the matrix while other proteins, e.g. COMP, were still found associated with the newly formed collagen network. The lack of collagen II induced changes in the expression profile of integrins. Further, we detected alterations in the Indian hedgehog/parathyroid hormone-related protein (Ihh/PTHrP) pathway that were accompanied by changes in the differentiation state of chondrocytes. Collagen II seems not to be essential for chondrocyte survival in culture but it plays an important role in maintaining chondrocyte differentiation. We suggest that a crosstalk between extracellular matrix and cells via integrins and the Ihh/PTHrP pathway is involved in regulating the differentiation state of chondrocytes.
authors: Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University , Jinan , China .
authors: Wei
authors: W
authors: Xin
authors: Juliane
authors: J
authors: Heilig
authors: Mats
authors: M
authors: Paulsson
authors: Frank
authors: F
authors: Zaucke
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D053823:Hedgehog Proteins; D016023:Integrins; D044162:Parathyroid Hormone-Related Protein; C514061:ihh protein, mouse
keywords: Cartilage extracellular matrix; chondrocyte; collagen; differentiation; integrin; knock down