The X-Linked Inhibitor of Apoptosis Protein Inhibitor Embelin Suppresses Inflammation and Bone Erosion in Collagen Antibody Induced Arthritis Mice.
OBJECTIVE
To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice.


METHODS
Four groups of mice (n = 6 per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells.


RESULTS
Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores (P < 0.05) and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 (P < 0.05) and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice.


CONCLUSIONS
Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss.
Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
Anak A S S K
AA
Dharmapatni
Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
Melissa D
MD
Cantley
School of Dentistry, University of Adelaide, Adelaide, SA 5005, Australia.
Victor
V
Marino
Medical Device Research Institute, School of Computer Science, Engineering and Mathematics, Flinders University, Bedford Park, SA 5042, Australia.
Egon
E
Perilli
Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
Tania N
TN
Crotti
Department of Rheumatology, Flinders Medical Centre and Flinders University, Bedford Park, SA 5042, Australia ; Rheumatology Research Unit, Repatriation Hospital, Daw Park, SA 5041, Australia.
Malcolm D
MD
Smith
Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
David R
DR
Haynes
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016227:Benzoquinones / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy* / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D000071681:Tartrate-Resistant Acid Phosphatase; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors*
D016227:Benzoquinones; D007527:Isoenzymes; D051636:X-Linked Inhibitor of Apoptosis Protein; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; C010945:embelin