Exp Mol Med.  2009 Sep;41(9):656-664. 10.3858/emm.2009.41.9.072.

Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells

• Kim D
• Kim SJ
• Kang SS
• Jin EJ

• KMID: 756209
• DOI: http://doi.org/10.3858/emm.2009.41.9.072

Abstract

Curcumin is a well known natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown. In the present report, we investigated the effects and signaling mechanism of curcumin on the regulation of chondrogenesis. Treating chick limb bud mesenchymal cells with curcumin suppressed chondrogenesis by stimulating apoptotic cell death. It also inhibited reorganization of the actin cytoskeleton into a cortical pattern concomitant with rounding of chondrogenic competent cells and down-regulation of integrin beta1 and focal adhesion kinase (FAK) phosphorylation. Curcumin suppressed the phosphorylation of Akt leading to Akt inactivation. Activation of Akt by introducing a myristoylated, constitutively active form of Akt reversed the inhibitory actions of curcumin during chondrogenesis. In summary, for the first time, we describe biological properties of curcumin during chondrogenic differentiation of chick limb bud mesenchymal cells. Curcumin suppressed chondrogenesis by stimulating apoptotic cell death and down-regulating integrin-mediated reorganization of actin cytoskeleton via modulation of Akt signaling.

Keyword

apoptosis; cell differentiation; chondrocytes; curcumin; cytoskeleton; microfilament; protooncogene proteins c-akt

MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
Apoptosis/drug effects
Cells, Cultured
Chick Embryo
Chondrogenesis/*drug effects
Curcumin/*pharmacology
Cytoskeleton/*drug effects/metabolism
Limb Buds/*cytology
Mesenchymal Stem Cells/cytology/*drug effects
Proto-Oncogene Proteins c-akt/metabolism