TY - JOUR
T1 - Glutamine metabolism modulates chondrocyte inflammatory response
AU - Arra, Manoj
AU - Swarnkar, Gaurav
AU - Adapala, Naga Suresh
AU - Naqvi, Syeda Kanwal
AU - Cai, Lei
AU - Rai, Muhammad Farooq
AU - Singamaneni, Srikanth
AU - Mbalaviele, Gabriel
AU - Brophy, Robert
AU - Abu-Amer, Yousef
N1 - Funding Information:
This work is supported by NIH/NIAMS R01-AR072623 (to YA), Biomedical grant from Shriners Hospital for Children (YA), P30 AR074992 NIH Core Center for Musculoskeletal Biology and Medicine (to YA), R01-AR076758 and R01-AI161022 (to GM). National Institute of Arthritis and Musculoskeletal and Skin Diseases AR072623 Yousef Abu-Amer National Institute of Arthritis and Musculoskeletal and Skin Diseases Shriners Hospitals for Children National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health AR074992 85160-STL-20 AR076758 AI161022 Yousef Abu-Amer Yousef Abu-Amer Gabriel Mbalaviele Gabriel Mbalaviele The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Funding Information:
This work is supported by NIH/NIAMS R01-AR072623 (to YA), Biomedical grant from Shriners Hospital for Children (YA), P30 AR074992 NIH Core Center for Musculoskeletal Biology and Medicine (to YA), R01-AR076758 and R01-AI161022 (to GM).
Publisher Copyright:
© Arra et al.
PY - 2022
Y1 - 2022
N2 - Osteoarthritis is the most common joint disease in the world with significant societal consequences but lacks effective disease-modifying interventions. The pathophysiology consists of a prominent inflammatory component that can be targeted to prevent cartilage degradation and structural defects. Intracellular metabolism has emerged as a culprit of the inflammatory response in chondrocytes, with both processes co-regulating each other. The role of glutamine metabolism in chondrocytes, especially in the context of inflammation, lacks a thorough understanding and is the focus of this work. We display that mouse chondrocytes utilize glutamine for energy production and anabolic processes. Furthermore, we show that glutamine deprivation itself causes metabolic reprogramming and decreases the inflammatory response of chondrocytes through inhibition of NF-κB activity. Finally, we display that glutamine deprivation promotes autophagy and that ammonia is an inhibitor of autophagy. Overall, we identify a relationship between glutamine metabolism and inflammatory signaling and display the need for increased study of chondrocyte metabolic systems.
AB - Osteoarthritis is the most common joint disease in the world with significant societal consequences but lacks effective disease-modifying interventions. The pathophysiology consists of a prominent inflammatory component that can be targeted to prevent cartilage degradation and structural defects. Intracellular metabolism has emerged as a culprit of the inflammatory response in chondrocytes, with both processes co-regulating each other. The role of glutamine metabolism in chondrocytes, especially in the context of inflammation, lacks a thorough understanding and is the focus of this work. We display that mouse chondrocytes utilize glutamine for energy production and anabolic processes. Furthermore, we show that glutamine deprivation itself causes metabolic reprogramming and decreases the inflammatory response of chondrocytes through inhibition of NF-κB activity. Finally, we display that glutamine deprivation promotes autophagy and that ammonia is an inhibitor of autophagy. Overall, we identify a relationship between glutamine metabolism and inflammatory signaling and display the need for increased study of chondrocyte metabolic systems.
UR - http://www.scopus.com/inward/record.url?scp=85136339644&partnerID=8YFLogxK
U2 - 10.7554/eLife.80725
DO - 10.7554/eLife.80725
M3 - Article
C2 - 35916374
AN - SCOPUS:85136339644
SN - 2050-084X
VL - 11
JO - eLife
JF - eLife
M1 - e80725
ER -