Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid.
OBJECTIVE
To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro.


METHODS
Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and (3)H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated (3)H-proline.


RESULTS
Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly.


CONCLUSIONS
These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.
Englert
Carsten
C
University of California, San Diego, La Jolla 92093-0412, USA.
McGowan
Kevin B
KB
Klein
Travis J
TJ
Giurea
Alexander
A
Schumacher
Barbara L
BL
Sah
Robert L
RL
D000818:Animals; D000831:Animals, Newborn; D002358:Cartilage, Articular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D009924:Organ Culture Techniques; D011392:Proline / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*; D000099158:Proteoglycan 4
D006133:Growth Substances; D006820:Hyaluronic Acid; D011392:Proline; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D011509:Proteoglycans; D012710:Serum Albumin, Bovine; C498836:PRG4 protein, Bos taurus; D000099158:Proteoglycan 4