Morin Disrupts Cytoskeleton Reorganization in Osteoclasts through an ROS/SHP1/c-Src Axis and Grants Protection from LPS-Induced Bone Loss

• Published in: Antioxidants Vol. 11; no. 5; p. 963
• Main Authors: Park, Hyun-Jung, Park, Jung-Nam, Yoon, Sun-Young, Yu, Rina, Suh, Jae-Hee, Choi, Hye-Seon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.05.2022; MDPI
• Subjects: Acid phosphatase (tartrate-resistant); Actin; Antibodies; Arthritis; Bone density; Bone loss; Bone marrow; Botulinum toxin; Computed tomography; Cytoskeleton; Flavonoids; Guanine; Guanine nucleotide exchange factor; Homology; Inflammation; inflammatory bone loss; Ligands; Lipopolysaccharides; morin; osteoclast; Osteoclasts; Oxidative stress; Phosphatase; Reactive oxygen species; SHP-1 protein; Src homology region 2 domain-containing phosphatase 1; Src protein; Tumor necrosis factor-TNF; United States > US; morin; Src homology region 2 domain-containing phosphatase 1; osteoclast; inflammatory bone loss; reactive oxygen species
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11050963

Morin is a naturally occurring flavonoid with anti-inflammatory and antioxidative properties. Therefore, we hypothesized that morin may prevent inflammatory bone loss by reducing oxidative stress. To investigate the effect of morin on inflammatory bone loss, mice were injected with lipopolysaccharide (LPS). Osteoclasts (OCs) were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and actin ring formation. Micro-computerized tomography analysis indicated that morin prevented LPS-induced bone loss in mice. In vivo TRAP staining indicated that morin decreased the number and surface of the OCs that were increased in LPS-treated mice. Furthermore, in vitro experiments indicated that morin decreased the number and activity of OCs upon LPS stimulation. Morin decreased actin ring-containing OCs with decreased activation of c-Src (Y416)/vav guanine nucleotide exchange factor 3/Ras-related C3 botulinum toxin substrate 1 compared with LPS alone. Morin decreased cytosolic reactive oxygen species (ROS), thus preventing the oxidation of Src homology region 2 domain-containing phosphatase 1 (SHP-1), followed by the inactivation of c-Src via direct interaction with SHP1. Conversely, SHP1 knockdown abolished the inhibitory effect of morin on OCs. Therefore, our findings suggest that morin disrupted cytoskeletal reorganization via an ROS/SHP1/c-Src axis in OCs, thereby granting protection from LPS-induced bone loss, which demonstrates its therapeutic potential against inflammatory bone loss.