활성 오스테오칼신 (ucOCN)이 TNF-α로 유도된 염증 반응을 억제하는 기전 규명
Undercarboxylated osteocalcin (ucOCN) suppresses TNF-α-induced expressions of inflammatory genes
- 주제(키워드) 도움말 osteocalcin , undercarboxylated osteocalcin , inflammation , TNFα , C2C12
- 발행기관 강릉원주대학교 일반대학원
- 지도교수 도움말 고성희, 백경화
- 발행년도 2016
- 학위수여년월 2016. 8
- 학위명 석사
- 학과 및 전공 도움말 일반대학원 치의학과
- 실제URI http://www.dcollection.net/handler/kangnung/000000008373
- 본문언어 한국어
초록/요약 도움말
Osteocalcin is one of the most abundant proteins synthesized and secreted in bone. Classically it’s been only understood to be a regulator of bone mineralization, but mounting evidence suggest a new endocrine role for osteocalcin that affects multiple aspects of glucose and energy metabolism during adulthood, male fertility and cognition. ESP, a tyrosine phosphatase expressed only in bone, negatively regulates the carboxylation of osteocalin. The inverse correlations between serum bioactive osteocalcin (ucOCN) and glucose metabolism in patients with obesity and/or type 2 diabetes has been reported. However, the role of ucOCN for regulation of inflammatory genes has not been studied. In the present study, we demonstrated 1) whether tumor necrosis factor α (TNFα), a major inflammatory cytokine, regulates osteocalcin expression and activation and 2) whether ucOCN has regulatory role for expression of inflammatory genes in C2C12 cells. The results showed that TNFα increases ESP expressions, while decreases OCN expression and ucOCN level. Increased ESP and suppressed OCN/ucOCN level was attenuated by inhibiting ERK, MAPK, JNK, NF-κB, TNFα downstream signaling pathways. TNFα induced expressions of IL-6, IL-1β, iNOS, TNFα and COX-2 were significantly suppressed by ucOCN (0.5, 5, 50 ng/ml) treatment. These results support a model in which, in the context of inflammatory diseases that increase the production of TNFα, TNFα downregulates the expression and activation of OCN/ucOCN through its downstream signaling pathways. The role of ucOCN in suppression of inflammatory gene expression was also demonstrated.
more목차 도움말
1. Introduction - 1 -
1.1. 염증 - 1 -
1.1.1. 염증의 병리학적 기전 - 1 -
1.1.2. 염증 표지 인자 - 2 -
1.1.2.1. Tumor necrosis factor α (TNFα) - 2 -
1.1.2.2. Interleukin-6 (IL-6) - 3 -
1.1.2.3. Interleukin-1 (IL-1) - 4 -
1.1.2.4. Cyclooxygenase-2 (COX-2) - 5 -
1.1.3. 염증 질환 - 6 -
1.1.3.1. 당뇨 - 6 -
1.1.3.2. 치주질환 - 6 -
1.1.3.3. 골관절염 - 7 -
1.1.4. 염증 조절 기전 연구의 현재 - 8 -
1.2. 골격계 - 10 -
1.2.1. 뼈의 대사 및 자가 조절 기능 - 10 -
1.2.2. 염증이 골 대사에 미치는 영향 - 11 -
1.3. Osteocalcin - 12 -
1.3.1. Osteocalcin (OCN) - 12 -
1.3.2. Osteocalcin의 내분비적 역할 - 13 -
1.4. 연구 목적 - 14 -
2. Materials and methods - 15 -
2.1. 세포배양 및 시약처리 - 15 -
2.2. mRNA 추출, cDNA 합성 및 Real time PCR - 16 -
2.3. Protein 추출 및 Western blot - 18 -
2.4. ELISA - 19 -
3. Results - 20 -
3.1. TNFα의 osteocalcin의 발현 조절 - 20 -
3.2. TNFα의 osteocalcin 발현 조절을 매개하는 하위 신호 전달 기전 - 21 -
3.3. Undercarboxylated osteocalcin (ucOCN)의 염증 조절 효과 확인 - 22 -
4. Discussion - 33 -
5. 참고문헌 - 36 -
6. 영문초록 - 43 -
