초록 ▼

1차년도: PKC에 의한 연골분화 조절 기구 즉
1) PKC 신호계에 의한 세포증식 조절,
2) PKC 신호계에 의한 세포부착 단백질의 발현 조절
3) PKC 신호계에 의한 세포응축과 연골결정 형성의 조절기구를 규명하였다.
2차년도: protein kinase cascade에 의한 PKC 신호전달계의 조절, 즉
1) PKA 등의 PKC 상위 신호전달계와 p38 MAP kinase등의 PKC 하위 신호전달계를 규명하였다.
3차년도: Protein kinase cascade와 분화관련 유전자의

1차년도: PKC에 의한 연골분화 조절 기구 즉
1) PKC 신호계에 의한 세포증식 조절,
2) PKC 신호계에 의한 세포부착 단백질의 발현 조절
3) PKC 신호계에 의한 세포응축과 연골결정 형성의 조절기구를 규명하였다.
2차년도: protein kinase cascade에 의한 PKC 신호전달계의 조절, 즉
1) PKA 등의 PKC 상위 신호전달계와 p38 MAP kinase등의 PKC 하위 신호전달계를 규명하였다.
3차년도: Protein kinase cascade와 분화관련 유전자의 확인과 기능규명 즉 proteome 분석에 의한 분화조절 단백질 확인하고 신호전달계에 의한 분화조절유전자 및 단백질의 발현과 활성 조절을 규명하였다.

Abstract ▼

Chondrogenic differentiation of mesenchymal cells is initiated by precartilage condensation which is characterized by cells being more densely packed in particular regions. Precartilage condensations differentiate into cartilage nodules where differentiated chondrocytes are located. However, the mol

Chondrogenic differentiation of mesenchymal cells is initiated by precartilage condensation which is characterized by cells being more densely packed in particular regions. Precartilage condensations differentiate into cartilage nodules where differentiated chondrocytes are located. However, the molecular mechanism, including the signal transduction involved in the regulation of chondrogenesis, has yet to be clearly elucidated. This project was, therefore, aimed to elucidate signaling pathways leading to chondrocytes differentiation by using micromass culture of chick limb bud mesenchymal celss as a model system. We were able to demonstrate that chondrogenic differentiation of chick 1 imb hut mesenchymal cells is regulated by complex. protein kinasa signaling cascades that include protein kinase C (PKC), Erk-1, p38 mitogen-activated protein (HAP) kinase, and protein kinase A. P7C appears to positively regulate chondrogenesis of mesenchymal cells. The PKC multigene family consists of 11 known isoforms, and multiple PKC isoforms such as α, ε, ζ, and λ/ι are expressed in differentiating chick 1 imb mesenchymal cells. Most evident among the expressed PKCisoforms during chondrogenesis is the increased expression and activation of PKC α, Whereas the selective inhibition Of down-regiulation of PKC α is sufficient to block chondrogenesis. This suggest a pivotal role of PKCα in chondrogenesis. PKC regulates both proliferation of chondrogenic competent cells and expression of cell adhesion molecules such as N-cadherin, fibronectin, and its receptor α5β1 integrin. The PKC-dependent regulation of chondrogenesis, including the expression of col 1 adhesion molecules, appears to be exerted via HAP kinase subtype Erk-1 signaling. It has been demonstrated that increased expression and activation of PKC were required for down-regulation of Erk-1 activity that correlated with the induction of chondrogenic differentiation of mesenchymal cells. In contrast to Erk-1, p38 MAP kinase activity was increased during chondrogenesis in a PKC-independent manner, and inhibition titan of p38 MAP kinase blocked chondrogenesis. Our results also indicated the involvement of PKA in PKC α -mediated regulation of chondrocyte differentiation. PKA appears to regulate chondrogenesis by activating PKC α , without modulation of its expression, at the stage of post-precartilage condensation. finally, we were able to elucidate molecular mechanism of EGF-induced inhibition of chondrocyte differentiation. Our data indicated that EGF negatively regulate chondrogenesis of chick limb buds mesenchymal cells by inhibiting precartilage lace condensation and by modulating signaling pathways including those of PKC α , Erk-1, and p38 mitogen-activated protein kinase.

목차 Contents

• 제 1 장 서론...8
• 제 1 절 연구개발의 필요성...8
• 제 2 절 연구목적 및 범위...9
• 제 2 장 국내외 기술개발 현황...11
• 제 3 장 연구개발수행 내용 및 결과...14
• 제 1 절 연구방법...14
• 제 2 절 주요연구결과...17
• 제 4 장 연구개발목표 달성도 및 대외기여도...38
• 제 5 장 연구개발결과의 활용계획...39
• 제 6 장 참고문헌...40