USULAN PENELITIAN

HUBUNGAN ANTARA DERAJAT NYERI DAN KADAR CARTILAGENOUS

OLIGOMERIC MATRIX PROTEIN DENGAN BONE MINERAL DENSITY

PADA WANITA PENDERITA OSTEOARTHRITIS LUTUT SIMTOMATIS

POST MENOPOUSE

Oleh :

Priza Razunip

PROGRAM PENDIDIKAN DOKTER SPESIALIS I

SUB BAGIAN / SMF ORTHOPAEDI DAN TRAUMATOLOGI

FAKULTAS KEDOKTERAN UNIVERSITAS UDAYANA

RSUP SANGLAH DENPASAR

2019
Cartilage Oligomeric Matrix Protein (COMP)

Since the earliest pathological changes in OA take place periarticularly, they are
not captured well by radiographs but are evident only through the costly MRI.
Therefore, the field of OA study is in desperate need of biomarkers which can change
the process of OA prediction, OA management, and the efficacy of drug therapies and
our understanding of disease pathogenesis. The possibility to objectively determine the
OA status through serum would significantly increase the possibilities of diagnosing
the disease with greater ease and with much cost-effective method than radiographic
methods (Verma, 2013).
A biomarker is a compound that is objectively measured and evaluated as an
indicator of normal biologic processes, pathogenic processes, or pharmacologic
responses to a therapeutic intervention. Biomarkers are not only essential for the
understanding of pathological pathways but also for diagnosis, prognosis and follow up
(Henrotin, 2016). During turnover of cartilage matrix in normal and diseased joints,
fragments of extracellular matrix molecules, and other degradation products of cartilage
metabolism are released into the synovial fluid and thereafter into the blood serum. One
such biomarker is COMP, which is an important degradation product of articular
cartilage and it may prove to be a promising diagnostic and prognostic marker in serum
for diagnosis of knee OA (Verma, 2013).
COMP is a 524-kd pentameric glycoprotein related to the thrombospondin
family and found predominantly in cartilage, although recent studies have identified
COMP in both tendon and synovium (Clark, 1999; Liang, 2015). COMP pentamer
bound up to five collagen molecules thereby retaining them in close proximity. By this
process, COMP facilitates the collagen–collagen interactions and microfibril
formation. Several studies conducted in past suggested that COMP is mainly produced
by articular chondrocytes and reached the consensus that COMP levels in synovial fluid
and serum might be related to cartilage damage (Verma, 2013).
COMP is abundantly expressed in articular cartilage as well as in proliferative
and hypertrophic chondrocytes of the growth plate, implicating its importance in
endochondral ossification and development of articular cartilage. COMP was first
known to interact with ECM proteins such as collagens, aggrecan, chondoitin sulfates,
fibronectin, and matrillin, and acts as a bridge between these molecules on the account
of its multi-domain modular structure. Following is an account of its interactions with
various ECM constituents. It forms an integral part of the cartilage extracellular matrix
(ECM), and its increase is related to reduced type IX collagen, matrilin-3 deposition
and also reduced overall matrix formation and increased chondrocyte death (Acharya,
2014).
Serum COMP value is significantly elevated in those suffering from knee
osteoarthritis than in normal population, 2) There is an insignificant gender bias in
serum COMP values in diseased or normal population, 3) Serum COMP value tend to
increase with increasing severity of disease (Singh, 2014). High sCOMP level also
reflects synovial inflammation in OA patients’ knees, as demonstrated by one study in
Bali. They found high sCOMP in 66% patients with synovial inflammation, as
compared to 33% in control group. High sCOMP was proven to be a significant risk
factor for synovial inflammation (adjusted-OR=3, p < 0.05), together with knee OA
severity (adjusted-OR=2.37, p < 0.05) and body mass index (adjusted OR=1.16, p <
0.05) (Martadiani, 2017). Among middle aged women, high sCOMP is associated with
increased risk of radiographic knee OA with overall OR of 1.97 (95% CI: 1.33–2.91)
over 20 years (Kluzek, 2015).
Serum COMP levels vary by ethnicity and sex. COMP was higher in African
American women than in Caucasian women (P = 0.003) and higher in Caucasian men
than Caucasian women (P = 0.0001). Possible differences in bone density and
metabolism, body composition, skeletal and joint size, cartilage and tendon mass, or
COMP levels in other organ systems could be potential explanations for the ethnic and
sex differences observed. The recent report of the presence of COMP in osteoblasts
suggests that differences in osteoblastic activity and expression of COMP could
possibly account for the ethnic and sex effects in COMP levels. Differences in s COMP
levels might also be related to differences in skeletal or joint size or to the total body
content of cartilage, meniscus, and tendon (Jordan, 2003).
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