Meniscal Tissue Degradation as the first sign of Osteoarthritis. THE PROCESS OF MECHANOTRANSDUCTION IN THE MENISCAL TISSUE. Barbara Zielinska Michigan University of Technology

Structure of the Meniscus C-shape (wedge-shape in cross-section profile) disks of fibro cartilage Interposed between the condyles of the femur and tibia Strong attachments to bone Inner 2/3 poor vacularization HUMAN KNEE – top view Photos from: Knee Meniscus- Basic and Clinical Foundations, 1992, Raven Press NY HUMAN KNEE – cross-section profile

Motivation Studies show that the meniscus is involved in the early stages of OA development. A better understanding of the loading environment and biochemical response of meniscal tissue may help us understand the etiology of OA.

Project definition FE model of medial partial meniscectomy MEASUREMENT OF THE CHANGES IN THE CONTACT PARAMETERS ON THE MENISCUS AFTER DIFFERENT PARTIAL MENISCECTOMIES Biochemical tests on the post incubated media MEASURMENTS OF THE AMOUNT OF VARIOUS MOLECULES RELEASED INTO THE MEDIA AFTER DIFFERENT LOAD CONDITIONS Real time RT-PCR MEASURMENT OF THE GENE EXPRESSION IN THE MENISCAL TISSUE AFTER DIFFERENT LOAD CONDITIONS

Clinical Treatment of Meniscal Tears Meniscal repair – Does not heal in avascular zone (Arnoczky, S.P. 1992; King, D. 1936) Allograft – Poor fixation technique – Difficulties with finding a donor of correct size (Paletta, G.A.,et al., 1997; Peters, G.A. et al.,2003; Felixs, N.A. & Paulos, L.E., 2003) Partial meniscectomy – Changes in contact area and stress distribution contribute to osteoarthritis (OA) (Baratz, M.E. et. al., 1986; Fukubayashi, T. & Kurosawa, H., 1980; Cole, B.J., 2004; Rangger, C., et al., 1995; Cox, J.S., et a;., 1975; Wyland, D.J., et a;., 2002; Fahmy, N.R.J et al., 1983) DIFFERENT TYPE OF TEARS Horizontal Radial Bucket-handle Photos from: Knee Meniscus- Basic and Clinical Foundations, 1992, Raven Press NY

Aims of the study Examine changes in contact parameters on superior surface of meniscus after medial meniscectomy. Examine changes on lateral meniscus after medial meniscectomy.

Finite Element Model Finite Element Model FRONT VIEW TOP VIEW FEMUR FEMUR CARTILAGE TIBIA CARTILAGE MEDIAL MENISCUS LATERAL MENISCUS TIBIA Donahue, T.L., et al., A finite element model of the human knee joint for the study of tibio-femoral contact. J Biomech Eng, (3): p

Simulations of Medial Partial Meniscectomies 5 % 10 % 30 % ANT-CENTCENTPOST-CENTPOST ANT-CENTPOST-CENT 60 % ANT-CENT-POST

Intact Case MEDIAL MENISCUS, SUPERIOR SIDE MAX L3= 9 % MAX CP = [MPa] MEAN CP = [MPa] CONTACT PRESSURE (CP)AXIAL STRAIN (LE3) POSTERIOR ANTERIOR

Measurement of GAGs Release of GAGs into the media after load from tissue explants is a sign of tissue matrix destruction.

Measurement of PGE 2 PGE 2, an intracellular signaling molecule, is high in patients with OA and is necessary in the cell death process.

Real time RT-PCR Measurement of Collagen, COX-2 and MMPs gene expression. – COX-2 is responsible for elevation of the PGE 2 level – MMPs- enzymes which are capable of collectively degrading all kinds of extracellular matrix proteins