Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25.
We have previously identified megakaryocyte stimulating factor (MSF) gene expression by synovial fibroblasts as the origin of lubricin in the synovial cavity. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage. MSF has a significant homology to vitronectin and is composed of 12 exons. RNA was purified from human synovial fibroblasts and articular chondrocytes grown in vitro from tissue explants obtained from subjects without degenerative joint disease. RT-PCR was used with multiple complimentary primer pairs spanning the central mucin expressing exon 6 of the MSF gene and individual exons on both the N- and C-terminal sides of exon 6. Exons 2, 4 and 5 appear to be variably expressed by synovial fibroblasts and articular chondrocytes. Lubricating mucin, in the form of MSF, is expressed by both chondrocytes and synovial fibroblasts in vitro. Both lubricin and superficial zone protein (SZP), a related proteoglycan, share a similar primary structure but could differ in post-translational modifications with O-linked oligosaccharides which are predominant in lubricin and with limited amounts chondroitin and keratan sulfate found in SZP. Since most of the MSF exons are involved in the expression of lubricating mucin, a strong homology to vitronectin persists. It is therefore appropriate to consider that both SZP and lubricin occupy a new class of biomolecules termed tribonectins. Screening of a human genome bacterial artificial chromsome (BAC) library with a cDNA primer pair complimentary for exon 6 identified two clones. Both clones were complimentary for chromosome 1q25 by in situ hybridization. This same locus was previously implicated in camptodactyl-arthropathy-pericarditis syndrome (CAP) by genetic mapping. It is hypothesized that CAP, a large joint arthropathy, may be associated with ineffective boundary lubrication provided by synovial fluid.
Jay
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The Department of Medicine, Rhode Island Hospital, Providence 02903, USA. gregory_jay_md@brown.edu
Tantravahi
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Britt
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Barrach
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CJ
D017398:Alternative Splicing / Q000235:genetics; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000032:analysis / Q000276:immunology; D022202:Chromosomes, Artificial, Bacterial; D002878:Chromosomes, Human, Pair 1; D002918:Chymotrypsin; D003001:Cloning, Molecular; D017931:DNA Primers; D005091:Exons; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology; D000099158:Proteoglycan 4
D000911:Antibodies, Monoclonal; D002809:Chondroitin Sulfates; D002918:Chymotrypsin; D017931:DNA Primers; D006023:Glycoproteins; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D000099158:Proteoglycan 4; C419197:PRG4 protein, human