Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies.
OBJECTIVE
Versican is the principal large proteoglycan expressed in mid-tendon, but its role in tendon pathology is unknown. Our objective was to define the expression of versican isoform splice variant messenger ribonucleic acid (mRNA) in normal Achilles tendons, in chronic painful tendinopathy and in ruptured tendons.


METHODS
Total RNA isolated from frozen tendon samples (normal n = 14; chronic painful tendinopathy n = 10; ruptured n = 8) was assayed by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for total versican, versican variants V0, V1, V2, V3 and type I collagen alpha1 mRNA, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Differences between sample groups were tested by Wilcoxon statistics.


RESULTS
Painful and ruptured tendons showed a significant decrease (median 2-fold) in the expression of versican mRNA, in contrast to an increased expression (median 8-fold) of type I collagen alpha1 mRNA in painful tendons. Versican splice variants V0 and V1 mRNA were readily detected in normal samples, V3 levels were substantially lower, and V2 levels were more variable. Each of V1, V2 and V3 mRNA showed significant decreases in expression in painful and ruptured tendons, but V0 was not significantly changed.


CONCLUSIONS
Changes in versican expression relative to that of collagen, and alterations in the balance of versican splice variants, may contribute to changes in matrix structure and function in tendinopathies.
Corps
A N
AN
Rheumatology Research Unit, Box 194, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. anc@mole.bio.cam.ac.uk
Robinson
A H N
AH
Movin
T
T
Costa
M L
ML
Ireland
D C
DC
Hazleman
B L
BL
Riley
G P
GP
D000125:Achilles Tendon / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics; D006801:Humans; D037181:Lectins, C-Type; D008875:Middle Aged; D010146:Pain / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D052256:Tendinopathy / Q000235:genetics*; D013708:Tendon Injuries / Q000235:genetics*; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; C508322:VCAN protein, human; D053675:Versicans