Analysis of meniscal degeneration and meniscal gene expression.
BACKGROUND
Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells.


METHODS
Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR.


RESULTS
The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and prostaglandin E synthase (PTGES), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific.


CONCLUSIONS
Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA.
Sun
Yubo
Y
Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC 28232, USA. yubo.sun@carolinas.org
Mauerhan
David R
DR
Honeycutt
Patrick R
PR
Kneisl
Jeffrey S
JS
Norton
James H
JH
Hanley
Edward N
EN
Gruber
Helen E
HE
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; D018836:Inflammation Mediators; D012333:RNA, Messenger