Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling

Abstract Background Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however,...

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Autores principales:	Lixia Zhang, Cameron L. Kirkwood, Jiho Sohn, Ashley Lau, Mary Bayers-Thering, Supinder Kour Bali, Sridhar Rachala, John M. Marzo, Mark J. Anders, Frank Beier, Keith L. Kirkwood
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Osteoarthritis Myeloid-derived suppressor cells Osteoclasts Obesity Subchondral bone Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/25352de7e5a5423e8bab737e355eecad
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spelling	oai:doaj.org-article:25352de7e5a5423e8bab737e355eecad2021-11-21T12:03:43ZExpansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling10.1186/s13075-021-02663-z1478-6362https://doaj.org/article/25352de7e5a5423e8bab737e355eecad2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13075-021-02663-zhttps://doaj.org/toc/1478-6362Abstract Background Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. Results We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. Conclusion These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.Lixia ZhangCameron L. KirkwoodJiho SohnAshley LauMary Bayers-TheringSupinder Kour BaliSridhar RachalaJohn M. MarzoMark J. AndersFrank BeierKeith L. KirkwoodBMCarticleOsteoarthritisMyeloid-derived suppressor cellsOsteoclastsObesitySubchondral boneDiseases of the musculoskeletal systemRC925-935ENArthritis Research & Therapy, Vol 23, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Osteoarthritis Myeloid-derived suppressor cells Osteoclasts Obesity Subchondral bone Diseases of the musculoskeletal system RC925-935
spellingShingle	Osteoarthritis Myeloid-derived suppressor cells Osteoclasts Obesity Subchondral bone Diseases of the musculoskeletal system RC925-935 Lixia Zhang Cameron L. Kirkwood Jiho Sohn Ashley Lau Mary Bayers-Thering Supinder Kour Bali Sridhar Rachala John M. Marzo Mark J. Anders Frank Beier Keith L. Kirkwood Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
description	Abstract Background Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. Results We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. Conclusion These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.
format	article
author	Lixia Zhang Cameron L. Kirkwood Jiho Sohn Ashley Lau Mary Bayers-Thering Supinder Kour Bali Sridhar Rachala John M. Marzo Mark J. Anders Frank Beier Keith L. Kirkwood
author_facet	Lixia Zhang Cameron L. Kirkwood Jiho Sohn Ashley Lau Mary Bayers-Thering Supinder Kour Bali Sridhar Rachala John M. Marzo Mark J. Anders Frank Beier Keith L. Kirkwood
author_sort	Lixia Zhang
title	Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
title_short	Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
title_full	Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
title_fullStr	Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
title_full_unstemmed	Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
title_sort	expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling
publisher	BMC
publishDate	2021
url	https://doaj.org/article/25352de7e5a5423e8bab737e355eecad
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Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling

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