MicroRNA Profiling in Adipose Before and After Weight Loss Highlights the Role of miR‐223‐3p and the NLRP3 Inflammasome

Macartney-Coxson, Donia; Danielson, Kirsty; Clapham, Jane; Benton, Miles C.; Johnston, Alice S. A.; Jones, Angela L.; Shaw, Odette M.; Hagan, R. D.; Hoffman, Eric P.; Hayes, Mark; Harper, Jacquie L.; Langston, Michael A.; Stubbs, Richard S.

doi:10.1002/oby.22722

Cited by 13 publications

(7 citation statements)

References 44 publications

(61 reference statements)

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“…have observed downregulation of miR-223-3p expression in the omentum and subcutaneous adipose tissue after weight loss induced by a gastric bypass (43) .…”

Section: Discussionmentioning

confidence: 95%

Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice

Carvalho

Brooks

Barlow

et al. 2020

Journal of Bone and Mineral Research

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Opioid use is detrimental to bone health, causing both indirect and direct effects on bone turnover. While the mechanisms of these effects are not entirely clear, recent studies have linked chronic opioid use to alterations in circulating miRNAs. Our aim was to develop a model of opioid-induced bone loss to understand bone turnover and identify candidate miRNA-mediated regulatory mechanisms. We evaluated the effects of sustained morphine treatment on the skeleton, metabolism, and body composition of male and female C57BL/6J mice by treating with vehicle (0.9% saline) or morphine (18 mg/kg) using subcutaneous osmotic minipumps for 25 days. Morphine-treated mice had higher energy expenditure and respiratory quotient, indicating a shift toward carbohydrate metabolism. Microcomputed tomography (µCT) analysis indicated that male mice treated with morphine had reduced trabecular bone volume fraction (Tb.BV/TV) (15%) and Tb. bone mineral density (BMD) (14%) in the distal femur compared to vehicle.Conversely, bone microarchitecture was not changed in females after morphine treatment.Histomorphometric analysis demonstrated that in males, morphine reduced bone formation rate compared to vehicle, but osteoclast parameters were not different. Furthermore, morphine reduced bone formation marker gene expression in the tibia of males (Bglap and Dmp1).Circulating miRNA profile changes were evident in males, with 14 differentially expressed miRNAs associated with morphine treatment. Target analysis indicated hypoxia inducible factor (HIF) signaling pathway was targeted by miR-223-3p and fatty acid metabolism by miR-484, -223-3p, and -328-3p. In summary, we have established a model where morphine leads to a lower trabecular bone formation in males. Further, understanding the mechanisms of bone loss from opioid treatment will be important for improving management of the adverse effects of opioids on the skeleton..

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“…have observed downregulation of miR-223-3p expression in the omentum and subcutaneous adipose tissue after weight loss induced by a gastric bypass (43) .…”

Section: Discussionmentioning

confidence: 95%

Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice

Carvalho

Brooks

Barlow

et al. 2020

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Previous evidence shows that miR-223-3p is not only related to bone, but also with adipose tissue. Macartney-Coxson et al have observed downregulation of miR-223-3p expression in the omentum and subcutaneous adipose tissue after weight loss induced by a gastric bypass (43) .…”

Section: Discussionmentioning

confidence: 99%

Sustained morphine delivery suppresses bone formation and alters metabolic and circulating miRNA profiles in male C57BL/6J mice

Carvalho

Brooks

Barlow

et al. 2022

Preprint

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Opioid use is detrimental to bone health, causing both indirect and direct effects on bone turnover. While the mechanisms of these effects are not entirely clear, recent studies have linked chronic opioid use to alterations in circulating miRNAs. Our aim was to develop a model of opioid-induced bone loss to understand bone turnover and identify candidate miRNA-mediated regulatory mechanisms. We evaluated the effects of sustained morphine treatment on the skeleton, metabolism, and body composition of male and female C57BL/6J mice by treating with vehicle (0.9% saline) or morphine (18 mg/kg) using subcutaneous osmotic minipumps for 25 days. Morphine-treated mice had higher energy expenditure and respiratory quotient, indicating a shift toward carbohydrate metabolism. Microcomputed tomography (microCT) analysis indicated that male mice treated with morphine had reduced trabecular bone volume fraction (Tb.BV/TV) (15%) and Tb. bone mineral density (BMD) (14%) in the distal femur compared to vehicle. Conversely, bone microarchitecture was not changed in females after morphine treatment. Histomorphometric analysis demonstrated that in males, morphine reduced bone formation rate compared to vehicle, but osteoclast parameters were not different. Furthermore, morphine reduced bone formation marker gene expression in the tibia of males (Bglap and Dmp1). Circulating miRNA profile changes were evident in males, with 14 differentially expressed miRNAs associated with morphine treatment. Target analysis indicated hypoxia inducible factor (HIF) signaling pathway was targeted by miR-223-3p and fatty acid metabolism by miR-484, -223-3p, and -328-3p. In summary, we have established a model where morphine leads to a lower trabecular bone formation in males. Further, understanding the mechanisms of bone loss from opioid treatment will be important for improving management of the adverse effects of opioids on the skeleton.

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“…Another study found an association between miR-223-3p and NLRP3 inflammatory hyperactivation in obesity for the first time. In subcutaneous fat, a significant correlation was observed between miR-223-3p and miR-223-5p and glucose, NLRP3, and blood lipids (Macartney-Coxson et al 2020 ). In another study, the expression levels of miR-223-3p and NLRP3 were measured in glioblastoma tumor tissue.…”

Section: Nlrp3 Inflammasome As a Potential Target For Mir-223mentioning

confidence: 99%

miRNA-223 as a regulator of inflammation and NLRP3 inflammasome, the main fragments in the puzzle of immunopathogenesis of different inflammatory diseases and COVID-19

Houshmandfar

Saeedi-Boroujeni

Rashno

et al. 2021

Naunyn-Schmiedeberg's Arch Pharmacol

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Millions of people around the world are involved with COVID-19 due to infection with SARS-CoV-2. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing COVID-19 immunopathogenesis have remained uncertain. miR-223 is a hematopoietic cell-derived miRNA that is implicated in regulating monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses. The miR-223 controls inflammation by targeting a variety of factors, including TRAF6, IKKα, HSP-70, FOXO1, TLR4, PI3K/AKT, PARP-1, HDAC2, ITGB3, CXCL2, CCL3, IL-6, IFN-I, STMN1, IL-1β, IL-18, Caspase-1, NF-κB, and NLRP3. The key role of miR-223 in regulating the inflammatory process and its antioxidant and antiviral role can suggest this miRNA as a potential regulatory factor in the process of COVID-19 immunopathogenesis.

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MicroRNA Profiling in Adipose Before and After Weight Loss Highlights the Role of miR‐223‐3p and the NLRP3 Inflammasome

Cited by 13 publications

References 44 publications

Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice

Sustained Morphine Delivery Suppresses Bone Formation and Alters Metabolic and Circulating miRNA Profiles in Male C57BL/6J Mice

Sustained morphine delivery suppresses bone formation and alters metabolic and circulating miRNA profiles in male C57BL/6J mice

miRNA-223 as a regulator of inflammation and NLRP3 inflammasome, the main fragments in the puzzle of immunopathogenesis of different inflammatory diseases and COVID-19

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