Ablation of Y-1 receptor impairs osteoclast bone-resorbing activity

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Sousa, DM (Author) Other; Conceicao, F (Author) Other; Silva, DI (Author) Other; Leitao, L (Author) Other; Neto, E (Author) Other; Alves, CJ (Author) Other; Alencastre, IS (Author) Other; Herzog, H (Author) Other; Paulo Aguiar (Author) FMUP; Lamghari, M (Author) Other

Journal

Title: Scientific Reports

Vol. 6

ISSN: 2045-2322

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 14 Citations

Other information

Authenticus ID: P-00K-WNA

DOI: 10.1038/srep33470

Abstract (EN): Y-1 receptor (Y1R)-signalling pathway plays a pivotal role in the regulation of bone metabolism. The lack of Y1R-signalling stimulates bone mass accretion that has been mainly attributed to Y1R disruption from bone-forming cells. Still, the involvement of Y1R-signalling in the control of bone-resorbing cells remained to be explored. Therefore, in this study we assessed the role of Y1R deficiency in osteoclast formation and resorption activity. Here we demonstrate that Y1R germline deletion (Y1R-/-) led to increased formation of highly multinucleated (n > 8) osteoclasts and enhanced surface area, possibly due to monocyte chemoattractant protein-1 (MCP-1) overexpression regulated by RANKL-signalling. Interestingly, functional studies revealed that these giant Y1R-/- multinucleated cells produce poorly demineralized eroded pits, which were associated to reduce expression of osteoclast matrix degradation markers, such as tartrate-resistant acid phosphatase-5b (TRAcP5b), matrix metalloproteinase-9 (MMP-9) and cathepsin-K (CTSK). Tridimensional (3D) morphologic analyses of resorption pits, using an in-house developed quantitative computational tool (BonePit), showed that Y1R-/- resorption pits displayed a marked reduction in surface area, volume and depth. Together, these data demonstrates that the lack of Y(1)Rs stimulates the formation of larger multinucleated osteoclasts in vitro with reduced bone-resorbing activity, unveiling a novel therapeutic option for osteoclastic bone diseases based on Y1R-signalling ablation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11