title: Changes in matrix protein biochemistry and the expression of mRNA encoding matrix proteins and metalloproteinases in posterior tibialis tendinopathy.
abstract: OBJECTIVE
  Adult-acquired flat foot secondary to a dysfunctional posterior tibialis tendon (PTT) is often treated by surgical transfer of the flexor digitorum longus tendon (FDLT). In this study, the authors compared normal PTT, stage II dysfunctional PTT and replacement FDLT, aiming to define changes in collagen modification, glycosaminoglycan (GAG) and the expression of matrix and metalloproteinase mRNA.
  
  
  METHODS
  Normal PTTs were obtained from patients with no history of tendon problems. Samples of dysfunctional PTT and replacement FDLT tissue were obtained from patients undergoing surgical reconstruction. Tissue samples were analysed for total collagen and GAG, pentosidine and collagen cross-links. Total RNA was assayed for mRNA encoding matrix proteins and metalloproteinases, using real-time reverse transcription PCR. Differences between clinical groups were assessed using non-parametric statistics.
  
  
  RESULTS
  Dysfunctional PTT contained higher levels of GAG and lower levels of pentosidine than normal PTT or FDLT. In contrast, collagen in FDLT contained fewer ketoimine and more aldimine cross-links than either normal or dysfunctional PTT. mRNA encoding types I and III collagens, aggrecan, biglycan, matrix metalloproteinase (MMP)-2, -13 and -23, and a disintegrin and metalloproteinase (ADAM)-12L each showed increased levels in dysfunctional PTT compared with either normal PTT or (except MMP-13) FDLT. In contrast, MMP-3 and ADAM with thrombospondin domain (ADAMTS)-5 mRNA were lower in both dysfunctional PTT and FDLT than in normal PTT, while ADAMTS-1 mRNA was lower in dysfunctional PTT than in FDLT.
  
  
  CONCLUSIONS
  Stage II dysfunctional PTT shows biochemical and molecular changes consistent with a chronic remodelling of the extracellular matrix, rather than rupture, while the replacement FDLT resembles normal PTT in many, but not all, parameters.
authors.affiliation: Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Corps
authors.forename: Andrew H N
authors.initials: AH
authors.lastname: Robinson
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Harrall
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Avery
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Curry
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hazleman
authors.forename: Graham P
authors.initials: GP
authors.lastname: Riley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D052256:Tendinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013710:Tendons / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D003094:Collagen; D001120:Arginine; C062187:pentosidine; D045726:Metalloproteases; D008239:Lysine