Early elevation of transforming growth factor-beta, decorin, and biglycan mRNA levels during cartilage matrix restoration after mild proteoglycan depletion.
OBJECTIVE
To elucidate the role of transforming growth factor-beta (TGF-beta) and the small proteoglycans biglycan and decorin in the repair of articular cartilage after proteoglycan depletion.


METHODS
Limited and reversible proteoglycan depletion was induced by injection of murine knee joints with 0.5% papain. Proteoglycan content of patellar cartilage was examined by safranin O staining on histological sections and overall proteoglycan synthesis was measured by incorporation of 35S sulfate. Changes in mRNA expression of TGF-beta, aggrecan, decorin, and biglycan were determined by semiquantitative reverse transcription polymerase chain reaction.


RESULTS
Papain injection led to rapid depletion of proteoglycans, which was partly overcome 7 days after injection, while total replenishment of the cartilage matrix with proteoglycans was observed on Day 24. The incorporation of radiolabeled sulfate in patellar proteoglycans was initially decreased (up to Day 3), but significantly enhanced on Days 4 and 7 after papain injection. Upregulation of TGF-beta, decorin, and biglycan mRNA in patellar cartilage was observed on Day 2, markedly before elevation of overall proteoglycan synthesis. mRNA levels were less augmented on Day 7, and on Day 24 all messenger RNA levels had returned to control values. As well, in the soft tissue adjoining the patella swift upregulation of TGF-beta mRNA was observed.


CONCLUSIONS
mRNA of both TGF-beta and the small proteoglycans decorin and biglycan are elevated at an early phase during cartilage repair after moderate proteoglycan depletion, implying a functional role for these molecules in this repair process.
van der Kraan
P M
PM
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Glansbeek
H L
HL
Vitters
E L
EL
van den Berg
W B
WB
D053674:Aggrecans; D000818:Animals; D058578:Biglycan; D002358:Cartilage, Articular / Q000737:chemistry / Q000502:physiology*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins; D007719:Knee Joint / Q000737:chemistry; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010206:Papain / Q000494:pharmacology; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D012038:Regeneration; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
C508320:Acan protein, mouse; D053674:Aggrecans; C546885:Bgn protein, mouse; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D010206:Papain