Clinical and Technical Review - Tecomedical

More documents

Recommendations

Info

10 Cartilage Degradation Chrondocyte: Chondroblasts trapped in lacunae develop into chondrocytes. Chondrocytes are important in the control of matrix turnover through production of collagen, proteoglycans and enzymes for cartilage metabolism. Proteins Matrix metalloproteinases: Are involved in the cleavage of Type II Collagen and the proteoglycan aggrecan. Three collagenases (MMP-1, -8,-13) are mainly responsible for primary cleavage of Type II Collagen. MMP-1, -8, -13 and 14 are involved in cleavage of the core protein of aggrecan. Cathepsin K: Protease produced by synovial fibroblasts, enzyme plays critical role in cartilage degradation (together with matrix metalloproteinases). MMPs perform extracellular predigestion of collagen, after endocytosis of large fragments, Cathepsin K degrades collagen and aggrecan in acidic lysosomes. Aggrecanases: Enzymes involved in cleavage of aggrecan. COMP: Cartilage Oligomeric Matrix Protein is an abundant cartilage glycoprotein also found in tendon and other tissues. Synthesized by chondrocytes, synovial and other skeleton cells. Intact and fragmented COMP in synovial fluid or serum is correlating to cartilage degradation in OA and RA. Cartilage metabolites and epitopes CTX-II: A 6 amino acid sequence epitope of the nonhelical C- terminal telopeptides resulting from Type II collagen degradation. C2C: C2C or COL2-3/4CLong epitope that specifically appears into circulation when Type II collagen degradation occurs. C1,2C: C1, 2C or COL2-3/4CShort epitope that appears into circulation when Type II but also Type I collagen degradation occurs. CS-GAG: Chondroitin sulfate glycosaminoglycans are bound at high densities, to a core protein forming the cartilage proteoglycan aggrecan molecule. Cartilage Synthesis Cartilage metabolites and epitopes Type II Procollagen: Secreted precursor of Type II Collagen. Extracellular cleavage results in N- and C-terminal propeptides. CP-II: Epitope of C- terminal propeptide, released during maturation of Type II Procollagen to Type II Collagen. Type II Collagen: The principal structural component of cartilage is an extensive network of Type II collagen molecules, arranged in fibrils. Collagen molecules consist of three chains to form a triple helix. Crosslinks between the chains and the molecules of collagen give collagen its strength. Proteoglycan Aggrecan: Responsible for the compressive strength of cartilage. Serve to trap and hold water to regulate matrix hydration. Monomer looks like test tube brush with keratan and chondroitin sulphate chains (= GAGs) bound to a protein core molecule. Monomers are attached via a link protein to hyaluronic acid. CS-GAG: Chondroitin sulfate glycosaminoglycans are bound at high densities, to a core protein forming the cartilage proteoglycan aggrecan molecule. Aggrecan epitope CS 846: Chondroitin native epitope, present on intact bioactive (“fetal-like”) proteoglycan only. PIINP: Epitope of Type II N-terminal propeptide, released during maturation of Type II Procollagen to Type II Collagen. PIINP has been postulated to play a role in chondrogenesis. It has been found to be synthesized by osteoarthritic chondrocytes in diseased cartilage and may serve as a specific arthritis biomarker that reflects an attempt by the chondrocytes to repair diseased cartilage. Proteins BMP1: BMP1 (Bone morphogenetic protein) is a protein that is capable of inducing formation of cartilage in vivo. It cleaves the C-terminal propeptides of procollagen I, II, and III and plays an important role in collagen maturation.
Biomarker according to NIH Osteoarthritis Biomarker Network Synovium Type III collagen Noncollagenous proteins Enzymes Aggrecan Type II collagen Cartilage Noncollagenous proteins Enzymes Proliferation/Formation Degradation PIIINP anti-CCP COMP Hyaluronan Pentosidine YKL-40 MMPs TIMPs Chondroitin sulfate PIICP PIINP PIIANP YKL-40 TIMPs Detailed information cartilage metabolism "Biomarker for diagnosis and monitoring of degenerative joint diseases" by Petra Seebeck, PhD, Glc-Gal-PYD PYD Keratan sulfate GAGs C1, 2C C2C COL2-1 COL2-1NO2 CTX-II HELIX II TIINE COMP CILP MMPs ADAMTSs Cathepsin K Inflammation marker – synovial metabolism Joint inflammation is a key feature of RA but can occur also during OA. Proliferative synovial inflammation leads to the forced syntheses of different marker. However, most of them are not synovium-specific, since they are also produced in cartilage and other tissues. anti-CCP Citrullin arises from enzymatic modification of the amino-acid arginine for instance during inflammatory processes. Auto-antibodies against cyclic citrullinated peptides (anti-CCP) were detected in up to 80%of RA patients already during a very early stage of disease, but only in very little patients with juvenile idiopathic arthritis (JIA). The concentrations of anti-CCP were not correlated to the disease activity score (DAS28), but to radiographic signs of joint destruction. Anti-rheumatic immunosuppressive therapy (Infliximab) reduced the sanguineous anti-CCP level in RA patients. Hyaluronan Hyaluronan is a main component of the cartilage matrix as well as the synovial fluid. In patients with knee OA the serological hyaluronan level correlated with the degree of synovial proliferation and the length of osteophytes but not with the femoral cartilage thickness. Increased hyaluronan levels were observed in OA as well as RA patients with patients with higher initial values showing a more progressive course of disease. Serological hyaluronan levels correlated with the degree of joint space narrowing. RA patients with synovial inflammation showed decreasing hyaluronan concentrations after anti-inflammatory therapy. 11
Page 1 and 2: Author: Peter Haima, Ph Clinical an
Page 3 and 4: Figure 1: Soloway 0 = Patients with
Page 5 and 6: Bone Resorption Osteoclast: Large m
Page 7 and 8: Bone Turnover - Biochemical Marker
Page 9: Bone marker and their behavior in v
Page 13 and 14: Cartilage Synthesis - Biochemical M
Page 15 and 16: Cartilage Biomarker and their behav
Page 17 and 18: Bonemarker normal values for childr
Page 19 and 20: Specific recommendations BAP Osteoc
Page 21 and 22: Bone marker - Reference values in a
Page 23 and 24: Cross reactivity - different specie

Clinical and Technical Review - Tecomedical

Create successful ePaper yourself

Delete template?

Save as template?