Mechanism of alveolar bone loss in a collagen-induced arthritis model in mice.
OBJECTIVE
the aim of this study was to understand the cellular/molecular mechanisms of periodontal breakdown in a collagen-induced arthritis (CIA) model in mice to enhance the understanding of rheumatoid arthritis (RA)-associated alveolar bone loss in humans.


METHODS
all analyses were performed on paired samples from CIA and control group mice. Mandibles were retrieved for micro-computed tomography (micro-CT), histomorphometric analysis, and isolation of alveolar bone cells (ABCs). In vitro osteoclastogenic/osteogenic/adipogenic potentials of ABCs were evaluated and the mRNA expression of downstream effector genes was assessed. Bone formation of ABCs was assessed using an ectopic transplantation model.


RESULTS
histomorphometric and micro-CT data showed that alveolar bone loss was significantly increased in the CIA group (p<0.05). Osteoclastogenesis was significantly increased in the CIA group in vivo (p<0.05), with upregulated mRNA expressions of osteoclastogenesis-associated genes. Osteoblasts appeared to undergo increased apoptosis, and the bone-forming activity of ABCs concomitantly decreased with in vitro osteogenic differentiation and in vivo ectopic transplantation (p<0.05). Also, adipogenesis-associated mRNA expression was highly expressed in the CIA group, resulting in significantly enhanced adipocyte differentiation in vitro (p<0.05).


CONCLUSIONS
these data demonstrate that increased osteoclastic activity, decreased bone-forming activity and enhanced adipogenesis promote alveolar bone loss in a CIA model in mice, and they suggest that these mechanisms could account for the same outcome in human RA.
Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
Jung-Chul
JC
Park
Chuanxin
C
Su
Im-Hee
IH
Jung
Seong-Ho
SH
Choi
Kyoo-Sung
KS
Cho
Chong-Kwan
CK
Kim
Yong-Beom
YB
Park
Soo-Kon
SK
Lee
Chang-Sung
CS
Kim
D050156:Adipogenesis / Q000502:physiology; D016301:Alveolar Bone Loss / Q000150:complications* / Q000473:pathology; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen; D004195:Disease Models, Animal; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology; D016555:Matched-Pair Analysis; D051379:Mice; D010010:Osteoclasts / Q000473:pathology*; D010012:Osteogenesis / Q000502:physiology*; D055114:X-Ray Microtomography / Q000662:veterinary
D003094:Collagen