DOS Kongressen 2014 ·
127
Collagen type IV in Articular Cartilage Damage and
Repair
Casper Bindzus Foldager, Wei Seong Toh, Bjørn Borsøe Christensen, Martin Lind,
Andreas H. Gomoll, Myron Spector
Orthopaedic Research Lab, Aarhus University Hospital; Faculty of Dentistry,
National University of Singapore; Sports Trauma Clinic, Aarhus University
Hospital; Cartilage Repair Center, Brigham & Women’s Hospital; VA Tissue
Engineering Lab, Harvard Medical School
Background:
Chondrocytes are surrounded by a thin layer of pericellular matrix
(PCM). Collagen type IV (COL4) is present in the PCM of healthy chondro-
cytes. COL4 is composed of three of six different alpha-chains. Three of these
alpha-chains contain angiogenesis inhibiting domains in alpha-1 (arresten), al-
pha-2 (canstatin), and alpha-3 (tumstatin), but their presence in cartilage is
unknown.
Purpose / Aim of Study:
To identify the COL4 alpha-chains in cartilage and
describe its distribution of in cartilage damage and repair.
Materials and Methods:
In vitro: Human chondrocytes from 6 patients were
cultured in standard 21% oxygen and physiologic 1% oxygen for up to 6 days.
Quantitative gene expression analysis (RT-qPCR) was performed to confirm the
chondrogenic phenotype (Sox5, Sox6, Sox9) and to investigate the presence of
the different COL4 alpha-chains 1-6. In vivo: Distribution of collagen type IV
was investigated with immunohistochemistry in normal cartilage (human, n=5),
damaged cartilage (human, n=5), clinically failed repair (human, n=11), carti-
lage repair with 6-month follow-up (minipig, n=11).
Findings / Results:
COL4 expression in normal chondrocytes consisted of alpha
chain 1 and 2. In normal cartilage COL4 was restricted to the PCM. Damaged
cartilage contained significantly less COL4 in the PCM compared with normal
cartilage. In minipigs with fibrous repair matrix COL4 was found in the extracel-
lular matrix (ECM) and not the PCM. In fibrocartilage COL4 was also seen in the
PCM and the interterritorial matrix. In hyaline repair tissue COL4 was restricted
to the PCM. In failed repair COL4 was found in the PCM of 0-75% of the cells
depending on tissue morphology and treatment.
Conclusions:
COL4 in cartilage contain the angiogenesis inhibitors arresten and
canstatin. The distribution of COL4 is changed in cartilage repair compared to
normal cartilage.
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