Formation and phenotype of cell clusters in osteoarthritic meniscus.
OBJECTIVE
To determine the histologic changes that accompany the formation of cell clusters during the early stages of osteoarthritis development in the meniscus, and to characterize the expression phenotype of these cells.


METHODS
Histologic sections of medial menisci from normal and anterior cruciate ligament (ACL)-deficient rabbit knees were immunolabeled with monoclonal antibodies for vimentin to highlight the cytoskeleton of meniscal cells, Ki-67 to identify proliferating cells, and type X collagen to evaluate changes in the cell expression phenotype. Tissue mineralization was assessed by specific staining with alizarin red.


RESULTS
Following ACL transection, there was an alteration in the normal interconnected network of meniscal cells in the fibrocartilaginous region of the tissue. This led to isolation of islands of cells within the extracellular matrix of the meniscal tissue. These islands of cells displayed 3 different morphologies based on cell composition: 1) stellate cells, 2) stellate as well as round cells, and 3) round cells. Islands composed solely of round cells were more prominent in the latter stages following ACL transection, and the size of these islands increased with time, apparently as the result of cell proliferation. These islands of cells corresponded to the "clusters" previously described in osteoarthritic cartilage. Strong expression of type X collagen colocalized with the deposition of calcium within the meniscal regions enriched with cell clusters.


CONCLUSIONS
Based on the observed changes in cell distribution, morphology, and cell proliferation as well as the previous detection of apoptosis in similar studies of rabbit knee joints, we propose a model for the development of cell clusters in the osteoarthritic meniscus. The morphologic appearance as well as the type X collagen expression phenotype of the meniscal cells forming the clusters is similar to that of hypertrophic chondrocytes. These findings provide a basis for understanding the origin of cell clusters in other joint connective tissues, such as osteoarthritic cartilage.
Hellio Le Graverand
M P
MP
University of Calgary, Alberta, Canada.
Sciore
P
P
Eggerer
J
J
Rattner
J P
JP
Vignon
E
E
Barclay
L
L
Hart
D A
DA
Rattner
J B
JB
D000818:Animals; D002113:Calcification, Physiologic; D002455:Cell Division; D048429:Cell Size; D003094:Collagen / Q000096:biosynthesis / Q000276:immunology; D018031:Connexin 43 / Q000032:analysis; D003599:Cytoskeleton / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000737:chemistry; D007150:Immunohistochemistry; D008592:Menisci, Tibial / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D008954:Models, Biological; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011817:Rabbits
D018031:Connexin 43; D003094:Collagen