Biomaterial Database

Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) attenuates remobilization-induced joint inflammation. 2020

Akinori Kaneguchi, and Junya Ozawa, and Kengo Minamimoto, and Kaoru Yamaoka

Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan.

Shortly after joint remobilization, inflammation is induced in the joint and aggravates joint contracture via subsequent fibrosis. However, the mechanisms involved in remobilization-induced inflammation are not yet fully understood. We hypothesized that joint immobilization followed by remobilization induces hypoxia/reoxygenation, initiating inflammatory reactions through nitric oxide (NO) production via NO synthase 2 (NOS2). This study aimed to investigate whether: 1) administration of the NOS inhibitor L-NG-nitroarginine methyl ester (l-NAME) can attenuate remobilization-induced joint inflammation; and 2) hypoxia/reoxygenation is induced by joint immobilization and followed by remobilization. Unilateral knee joints of rats were immobilized using external fixators for three weeks. After removal of the fixation device, knees were allowed to move freely for one day (remobilization) with or without l-NAME administration. Without l-NAME administration, inflammatory reactions including joint swelling and inflammatory cell infiltration, edema, and upregulation of inflammatory mediator genes in the joint capsule were detected following upregulation of the NOS2 gene after remobilization. These remobilization-induced inflammatory reactions were partially attenuated by administration of l-NAME. Therefore, NOS2/NO elevation has potential as a novel treatment for remobilization-induced joint inflammation. Gene expression of the hypoxia marker hypoxia inducible factor-1α was upregulated after one day of remobilization, rather than after immobilization. These results suggest that upregulation of NOS2 by remobilization might be not due to hypoxia/reoxygenation.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007719	Knee Joint	A synovial hinge connection formed between the bones of the FEMUR; TIBIA; and PATELLA.	Superior Tibiofibular Joint,Joint, Knee,Joint, Superior Tibiofibular,Knee Joints,Superior Tibiofibular Joints,Tibiofibular Joint, Superior
D008297	Male		Males
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015854	Up-Regulation	A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.	Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D016207	Cytokines	Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.	Cytokine
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats
D017746	Joint Capsule	The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner SYNOVIAL MEMBRANE.	Synovial Folds,Synovial Plica,Synovial Plicae,Articular Capsule,Capsula Articularis,Synovial Capsule,Articular Capsules,Capsule, Articular,Capsule, Joint,Capsule, Synovial,Fold, Synovial,Joint Capsules,Plica, Synovial,Synovial Capsules,Synovial Fold
D052247	Nitric Oxide Synthase Type II	A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.	INOS Enzyme,Inducible NOS Protein,Inducible Nitric Oxide Synthase,NOS-II,Nitric Oxide Synthase II,Nitric Oxide Synthase, Type II,NOS II