| 研究実績の概要 |
Our first-year plan is as follows: Elucidating the molecular mechanism of Pyk2 on the ontogeny of osteoclasts and microglia in vitro, using Pyk2 inhibitor. Following the plan, we conducted molecular biology investigations into the effects of utilizing a target inhibitor of Pyk2, a convergence gene we discovered, on osteoclasts and microglia. We demonstrated that inhibiting Pyk2 in microglia enhances phagolysosomal activities against Aβ oligomers both in vitro. In vivo, the administration of the Pyk2 inhibitor led to an increased migration of microglia toward deposits in the brains of Iba-1 EGFP transgenic mice, accompanied by morphological activation, suggesting a heightened affinity for Aβ. Furthermore, we confirmed that Pyk2 inhibitor inhibited the osteoclast differentiation. In vitro, Pyk2 inhibition significantly impedes osteoclast differentiation and bone resorption. In a co-culture system comprising osteoblasts and osteoclasts, Pyk2 inhibitor effectively suppressed osteoclast differentiation, accompanied by a substantial increase in the transcriptional expression of Tnfrsf11b and Csf1 in osteoblasts.
|
