Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice

Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib...

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Autores principales:	Shingo Sugahara, Kaori Hanaoka, Takashi Emori, Nobuaki Takeshita, Yasutomo Fujii, Masaki Nakano, Takako Suzuki, Jun Takahashi, Yukio Nakamura
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Arthritis Osteoporosis Osteoclast/osteoblast biology Peficitinib Bone density Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0f3811cf2f52458db0d2eb57ee8a9f18
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spelling	oai:doaj.org-article:0f3811cf2f52458db0d2eb57ee8a9f182021-11-20T04:57:29ZPeficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice1347-861310.1016/j.jphs.2021.10.006https://doaj.org/article/0f3811cf2f52458db0d2eb57ee8a9f182022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1347861321001018https://doaj.org/toc/1347-8613Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.Shingo SugaharaKaori HanaokaTakashi EmoriNobuaki TakeshitaYasutomo FujiiMasaki NakanoTakako SuzukiJun TakahashiYukio NakamuraElsevierarticleArthritisOsteoporosisOsteoclast/osteoblast biologyPeficitinibBone densityTherapeutics. PharmacologyRM1-950ENJournal of Pharmacological Sciences, Vol 148, Iss 1, Pp 134-141 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arthritis Osteoporosis Osteoclast/osteoblast biology Peficitinib Bone density Therapeutics. Pharmacology RM1-950
spellingShingle	Arthritis Osteoporosis Osteoclast/osteoblast biology Peficitinib Bone density Therapeutics. Pharmacology RM1-950 Shingo Sugahara Kaori Hanaoka Takashi Emori Nobuaki Takeshita Yasutomo Fujii Masaki Nakano Takako Suzuki Jun Takahashi Yukio Nakamura Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
description	Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.
format	article
author	Shingo Sugahara Kaori Hanaoka Takashi Emori Nobuaki Takeshita Yasutomo Fujii Masaki Nakano Takako Suzuki Jun Takahashi Yukio Nakamura
author_facet	Shingo Sugahara Kaori Hanaoka Takashi Emori Nobuaki Takeshita Yasutomo Fujii Masaki Nakano Takako Suzuki Jun Takahashi Yukio Nakamura
author_sort	Shingo Sugahara
title	Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
title_short	Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
title_full	Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
title_fullStr	Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
title_full_unstemmed	Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
title_sort	peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/0f3811cf2f52458db0d2eb57ee8a9f18
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Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice

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