Beruflich Dokumente
Kultur Dokumente
PENDIDIKAN : Tamat Dokter Brevet Spesialis Penyakit Dalam Brevet Subspesialis Reumatologi Brevet Subspesialis Geriatri Doktor Guru Besar
1972 FKUI 1979 FKUI 1986 FKUI 1996 FKUI 2004 FKUI 2005 FKUI
ORGANISASI : Ketua Umum, Ikatan Reumatologi Indonesia, 1994 2005 President , Rheumatology Association of ASEAN 2001 2006 Ketua Bidang Sp Konsultan, Kolegium Ilmu Penyakit Dalam (KIPD), 2006- 2012
Pathogenesis of OA
Wear and tear ?
It is not necessarily age related It is asymmetrically distribution/ localized It is progress steadily The sign & symptoms of inflammation
Role of inflammation in OA, what is the evidence ? What are inflammatory factors that could possibly be involved in genesis of OA structural changes?
Osteoarthritis chondrocyte
Increase functions Type II collagen and aggrecan synthesis (early OA) Cell proliferation Catabolic cytokine production MMPs, TPA/plasmin IL-I receptor type 1, NOS/NO, Cox-2/PGE2 Apoptosis, Decrease functions Type II collagen and aggrecan synthesis (late OA) IL-1 receptor antagonist Response to IGF-1
Chondrocyte metabolism
Stimulation IGFs, TGF-beta, PDGF, EGF Bone morphogenic protein Cartilage derived morphogenic protein Growth factor Stimulation Gamma- Interferon TNF-alpha Prostaglandins Oxygen radicals, NO
IL-1, TNF-alpha, IL-17, FGFs, gamma interferon Leukemia inhibitory factor Glucocorticoid Pro-collagen fragments Inhibition
TIMPs
PA, plasmin
+
Pro-MMPs
Active-MMPs
Chondrocytes
+
NO +
+
Thiol, serine proteases, MT-MMPs
+
NO
Management of Osteoarthritis
Non-pharmacological therapy
Pharmacological therapy
Surgery
OA KNEE
Intracellular signalling
NOS NO
Plasmin
TGF-B IGF-1
Activation of MMPs
Collagenase
Collagen II Aggrecans
Hyaluronic acid
Conclusion
Non-pharmacological therapy is as important as pharmacological therapy, and should be used in all cases There are some evidences that SYSADOAs, eg. diacerein is effective in osteoarthritis, and when used for a long term period they might be able to modify cartilage structure (disease modifying osteoarthritis drugs: DMOADs).
Thank You