日時：	2024 年11 月8 日（金）15:30 - 17:00
場所：	京都大学 医生物学研究所 南部総合研究１号館 共同セミナー室３ http://www.kyoto-u.ac.jp/ja/access/campus/yoshida/map6r_b.html
演者：	Prof. Astrid D. Bakker Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
演題：	How bone cells distinguish between catabolic and non-catabolic mechanical stimuli

講演要旨

Lack of mechanical stimulation, e.g. bed-rest, and overloading, e.g. around illfitting
orthopaedic or dental implants, cause bone loss through activation of bone resorbing
osteoclasts by mechanosensitive bone cells. In contrast, bone cells subjected to physiological
mechanical loads inhibit osteoclast formation and activity. How bone cells distinguish
between catabolic and non-catabolic mechanical stimuli remains a mystery. Previously we
found that physiological mechanical stimulation may reduce the stimulating effect of
cytokines on osteoclastogenesis. How inflammatory factors, such as cytokines and
chemokines, affect the response of bone cells to (un)loading also remains to be discovered.
Low intensity mechanical stimuli corresponded to active Piezo1, SERCA2, and
inhibition of bone resorption. We also found lower protein levels of Ezrin in cultured human
bone cells that stimulated osteoclast formation upon supraphysiological loading compared to
those that did not. Ezrin regulates membrane tension and is activated by inflammation.
Membrane tension and inflammation both affect ephrin receptors (EPH). We have tested the
effect of unloading versus a 5 min stimulation with shear stress of physiological magnitude,
known to inhibit osteoclast formation in vitro, on EPH activity in cultured human primary
bone cells. EPHs that were differentially activated after 5 min of unloading were EPHA2,
EPHA3, EPHA5 (highest), EPHA7, EPHB1 and EPHB2, while at 15 min they were EPHA5,
EPHA7, EPHB1, EPHB2 and EPHB3 (highest). Our results suggests that daily mechanical
stimuli rapidly inactivate multiple EPHs. Ongoing experiments need to elucidate whether the
activity of EPHs is modulated by mechanical (un)loading of bone in vivo, by overloading and
inflammatory factors in vitro, and whether there is a causal relation between activation of
certain EPHs and stimulation of osteoclastogenesis.　　（Language:English）

 

連絡先：京都大学 医生物学研究所 安達 泰治 adachi[@]infront.kyoto-u.ac.jp