Andri WS OA 2016

Curriculum Vitae Name : Andri Reza Rahmadi, MD, Internist & Rheumatologist , M.Med Education :  Medical Doctor graduated 1997 F.Med UNPAD Bandung  Master of Medicine graduated 2003 UGM Yogyakarta  Internal Medicine specialist graduated 2008 F.Med UNPAD Bandung  Rheumatology consultant graduated 2013 F.Med UNPAD/RSHS Bandung Fellow :  IDI, PAPDI, IRA

PATHOPHYSIOLOGY OF OSTEOARTHRITIS

Andri Reza Rahmadi, MD, Internist & Rheumatologist, M.Med

Introduction  Definition :  Osteoarthritis (OA) is a degenerative disease of

diarthrodial (synovial) joints, characterized by  Breakdown of articular cartilage  and proliferative changes of surrounding bones

Osteoarthritis : Degenerative Disease

Osteoarthritis

Past and New  Past :  Non Inflamation  Wear and Tear  New :  Mediator inflamation  Multifactorial etiology

Epidemiology

Hasan Sadikin Hospital Bandung  2007 in Rheumatology Clinic  1297 patients, 74,48% OA  2012 in Rheumatology Clinic  3986 patients, 64,91% OA

Up to Date Until late 20th century

21st century

 •A passive consequence

 •A cell-driven mechanism

of tear and wear  A degenerative disease  •A cartilage disease  •An inevitable fate

based on soluble mediators  •A pro-inflammatory

disease  •A multiple-tissue disease

 •A biological challenge open

to therapeutic intervention

Normal Cartilage Matrix

Cartilage  Avascular  Low Oxigen  Metabolism : glycolysis anaerob, lactic acid  Ph : 7,1 – 7,2  Nutrition and Water : from Synovium and

Subchondran bone  Difusion process

Cartilage Component  Chondrocyte, produce :  Collagen  Proteoglycan

 Matrix exracellular :  Water 65%  Colagen type II, IV, IX, XVI and Proteoglycan 15-

25%

Proteoglycan = Agrecan  Glucosaminoglycan  Chondroitin sulfate  Ceratan sulfate  Hyaluronic acid

Turnover :  Collagen : half life 100 year  Agrecan : half life 3-24 year

Osteoarthritis Cartilage

Clasification    

PRIMARY Unknown etiology Degenerative Genetic

   

SECONDARY Known etiology Trauma Overuse

Genetic  Scientist have discovered 11 pieces of genetic

code linked  Half OA patient have it  The one with the strongest effect was

situated in the region GNL 3 gene which produces a protein with an important role in cell maintenance

Mechanical Aspect  Obese  Over use  Weight forcess  Stairs  Climb  Sport  Accident

 Trauma

Mechanical Aspect

Pathophysiology OA

Interaction  Chondrocyte and Matrix Intracelular  Mediated by Integrin in cell surface  Normal Condition : homeostatis  Abnormal condition : more deragradation  Abnormal signaling by Integrin  Produce degradative enzyme : chondrocyte  Dominant enzyme : metaloproteinase (MMP)

Proteinase Enzyme  Metallo proteinase (Dominant in OA)  Serine proteinase  Cystein proteinase  Aspartat proteinase.

Metaloproteinase :  Collagenase  Gelatinase  Stromeolysine  Other : A Disintegrin and metaloproteinase

with Trombospondin Motifs type-1 (ADAMTs)

Process  Trauma  Cell collagen damage  Stimuli for macrophage in synovial line cell  Active macrophage in synovial line  Produce inflamation mediators :  IL 1 β  IL 6  IL 17  TNF - α

Cytokine pro inflamation  IL-1 : damage chondrocyte  IL-1 receptor in cell surface in chondrocyte  IL -1 receptor antagonist (IL-1 ra) produced

from synovial tissue to inhibit this reacti0n  Balance chondrogenesis homeostasis

Pathology : Inflamation

Inhibitor Mechanism  New cell for regeneration : Chondroblast  Proliferation to chondrocyte  Condroblast produce inhibitory enzyme :  Tissue inhibitor of metalloproteinase (TIMPs) :  TIMP-1, TIMP-2, TIMP-3, and TIMP-4.  In OA patients : Low TIMP level

Growth Factor in OA  Produced by Cell Synovium + Chondrocyte  Compensation : active if protease enzyme  Help proliferation of chondroblast  Side effect : subchondral bone growth  Produce Osteophyte  Enhtesytis  Inflamation  Pain

Growth Factor :  Transforming Growth Factor (TGF)  Insuline Growth Factor (IGF)  Fibroblast Growth Factor (FGF)

Free Radical in OA  Stress Oxidative from Super Oxyde reaction  Go direct to the Inside to the chondrocyte cell  Damage mithochodrial cell  Faster Apoptosis process  Ageing  Damage chondrocyte cell  OA  Activate inflamation cascade

Summary  Osteoarthritis is adisease with low level

inflamation  Until now it is not known mechanism  OA have some Multifactorial Risk Factors  It ‘s need further research in OA to find other mechanism