Clinical and Technical Review - Tecomedical

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.