We have previously shown that p38 mitogen-activated protein kinase (MAPK) inhibitors, which block the production and action of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), are effective in models of bone and cartilage degradation. To further investigate the ro
Chondrogenesis induced by actin cytoskeleton disruption is regulated via protein kinase C-dependent p38 mitogen-activated protein kinase signaling
✍ Scribed by Young-Bin Lim; Shin-Sung Kang; Won Gun An; Young-Sup Lee; Jang-Soo Chun; Jong Kyung Sonn
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 197 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Disruption of the actin cytoskeleton in subconfluent mesenchymal cells induces chondrogenic differentiation via protein kinase C (PKC) α signaling. In this study, we investigated the role of p38 mitogen‐activated protein (MAP) kinase in the chondrogenic differentiation of mesenchymal cells that is induced by depolymerization of the actin cytoskeleton. Treatment of mesenchymal cells derived from chick embryonic limb buds with cytochalasin D (CD) disrupted the actin cytoskeleton with concomitant chondrogenic differentiation. The chondrogenesis was accompanied by an increase in p38 MAP kinase activity and inhibition of p38 MAP kinase with SB203580 blocked chondrogenesis. Together these results suggest an essential role for p38 MAP kinase in chondrogenesis. In addition, inhibition of p38 MAP kinase did not alter CD‐induced increased expression and activity of PKCα, whereas down‐regulation of PKC by prolonged exposure of cells to phorbol ester inhibited CD‐induced p38 MAP kinase activation. Our results therefore suggest that PKC is involved in the regulation of chondrogenesis induced by disruption of the actin cytoskeleton via a p38 MAP kinase signaling pathway. © 2002 Wiley‐Liss, Inc.
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