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PMID: 10085302 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Type IIA procollagen containing the cysteine-rich amino propeptide is deposited in the extracellular matrix of prechondrogenic tissue and binds to TGF-beta1 and BMP-2.

The Journal of cell biology ·Vol. 144 ·No. 5 ·1999-03-08 ·Pages 1069-80

Zhu Y, Oganesian A, Keene DR, Sandell LJ

Abstract

Type II procollagen is expressed as two splice forms. One form, type IIB, is synthesized by chondrocytes and is the major extracellular matrix component of cartilage. The other form, type IIA, contains an additional 69 amino acid cysteine-rich domain in the NH2-propeptide and is synthesized by chondrogenic mesenchyme and perichondrium. We have hypothesized that the additional protein domain of type IIA procollagen plays a role in chondrogenesis. The present study was designed to determine the localization of the type IIA NH2-propeptide and its function during chondrogenesis. Immunofluorescence histochemistry using antibodies to three domains of the type IIA procollagen molecule was used to localize the NH2-propeptide, fibrillar domain, and COOH-propeptides of the type IIA procollagen molecule during chondrogenesis in a developing human long bone (stage XXI). Before chondrogenesis, type IIA procollagen was synthesized by chondroprogenitor cells and deposited in the extracellular matrix. Immunoelectron microscopy revealed type IIA procollagen fibrils labeled with antibodies to NH2-propeptide at approximately 70 nm interval suggesting that the NH2-propeptide remains attached to the collagen molecule in the extracellular matrix. As differentiation proceeds, the cells switch synthesis from type IIA to IIB procollagen, and the newly synthesized type IIB collagen displaces the type IIA procollagen into the interterritorial matrix. To initiate studies on the function of type IIA procollagen, binding was tested between recombinant NH2-propeptide and various growth factors known to be involved in chondrogenesis. A solid phase binding assay showed no reaction with bFGF or IGF-1, however, binding was observed with TGF-beta1 and BMP-2, both known to induce endochondral bone formation. BMP-2, but not IGF-1, coimmunoprecipitated with type IIA NH2-propeptide. Recombinant type IIA NH2-propeptide and type IIA procollagen from media coimmunoprecipitated with BMP-2 while recombinant type IIB NH2-propeptide and all other forms of type II procollagens and mature collagen did not react with BMP-2. Taken together, these results suggest that the NH2-propeptide of type IIA procollagen could function in the extracellular matrix distribution of bone morphogenetic proteins in chondrogenic tissue.

MeSH Terms
Base Sequence Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins/metabolism Cartilage/embryology,metabolism Cysteine/analysis DNA Primers Extracellular Matrix/metabolism Fluorescent Antibody Technique Humans Microscopy, Immunoelectron Procollagen/chemistry,metabolism Protein Binding Protein Isoforms/chemistry,metabolism Recombinant Proteins/chemistry,metabolism Transforming Growth Factor beta/metabolism
Chemicals
BMP2 protein, human Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins DNA Primers Procollagen Protein Isoforms Recombinant Proteins Transforming Growth Factor beta recombinant human bone morphogenetic protein-2 Cysteine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhu Y
Washington University School of Medicine, Department of Orthopedic Surgery, St. Louis, Missouri 63110, USA.
Oganesian A
Keene D R
Sandell L J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.144.5.1069
Published
1999-03-08
Pages
1069-80
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2148200
Subset
IM
Grants
NIAMS NIH HHS · R01 AR036994 · United States
NIAMS NIH HHS · R01AR36994 · United States
External Links
PubMed source DOI: 10.1083/jcb.144.5.1069 PMC Full Text View journal details
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