Flrt2 is involved in fine-tuning of osteoclast multinucleation.

Abstract:

:Osteoclasts are multinucleated giant cells derived from myeloid progenitors. Excessive bone resorption by osteoclasts can result in serious clinical outcomes for which better treatment options are needed. Here, we identified fibronectin leucine-rich transmembrane protein 2 (Flrt2), a ligand of the Unc5 receptor family for neurons, as a novel target associated with the late/maturation stage of osteoclast differentiation. Flrt2 expression is induced by stimulation with receptor activator of nuclear factor-kB ligand (RANKL). Flrt2 deficiency in osteoclasts results in reduced hyper-multinucleation, which could be restored by RNAi-mediated knockdown of Unc5b. Treatment with Netrin1, another ligand of Unc5b which negatively controls osteoclast multinucleation through down regulation of RANKL-induced Rac1 activation, showed no inhibitory effects on Flrt2-deficient cells. In addition, RANKL-induced Rac1 activation was attenuated in Flrt2-deficient cells. Taken together, these results suggest that Flrt2 regulates osteoclast multinucleation by interfering with Netrin 1-Unc5b interaction and may be a suitable therapeutic target for diseases associated with bone remodeling. [BMB Reports 2019; 52(8): 514-519].

journal_name

BMB Rep

journal_title

BMB reports

authors

Shirakawa J,Takegahara N,Kim H,Lee SH,Sato K,Yamagishi S,Choi Y

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

514-519

issue

8

eissn

1976-6696

issn

1976-670X

pii

4625

journal_volume

52

pub_type

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