IL-1.ALPHA. Stimulation of Osteoclast Survival through the PI 3-Kinase/Akt and ERK Pathway.

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Osteoclasts, cells that resorb bone, die once fully differentiated. Several factors including interleukin-1 (IL-1) have been shown to regulate the survival of mature osteoclasts. However, information on the mechanism underlying the regulation of osteoclast survival has been limited. In this study, we investigated the mechanism for the IL-1-stimulated survival of osteoclasts. Treatment of purified osteoclasts with IL-1α led to activation of the serine-threonine kinases Akt and ERK. Blocking the activation of Akt with LY 294002, a specific inhibitor of the Akt up-stream molecule PI 3-kinase, or with an adenoviral vector for a dominant-negative form of Akt prevented the stimulation of osteoclast survival by IL-1α. PD 98059, a specific inhibitor of the ERK-activating kinase MEK 1, also abolished the effects of IL-1α on ERK activation and osteoclast survival. IL-1α reduced the apoptosis of osteoclasts by reducing caspase 3 activity. The IL-1α-mediated suppression of apoptosis was abolished by the PI 3-kinase/Akt or MEK1/ERK pathway inhibitor. These findings implicate the PI 3-kinase/Akt and ERK signaling pathways in the promotion of osteoclast survival by IL-1α.
社団法人日本生化学会の論文