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Morin Disrupts Cytoskeleton Reorganization in Osteoclasts through an ROS/SHP1/c-Src Axis and Grants Protection from
Hyun-Jung Park1, Jung-Nam Park1, Sun-Young Yoon1
1Department of Biological Sciences (BK21 Program), University of Ulsan, Ulsan 44610, Korea.
Abstract:
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.
Insights
Morin, a flavonoid, prevents inflammatory bone loss by reducing oxidative stress and inhibiting osteoclast activity. It targets the ROS/SHP1/c-Src pathway, showing therapeutic potential for bone conditions.
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Morin is a flavonoid with known anti-inflammatory and antioxidative properties.
- Inflammatory bone loss is a significant clinical concern, often linked to oxidative stress.
Purpose of the Study:
- To investigate the potential of morin in preventing inflammatory bone loss.
- To elucidate the molecular mechanisms underlying morin's effects on osteoclasts.
Main Methods:
- Lipopolysaccharide (LPS)-induced bone loss model in mice.
- Analysis of osteoclast differentiation and activity using TRAP staining and actin ring formation assays.
- Assessment of intracellular signaling pathways, including reactive oxygen species (ROS) and c-Src activation.
Main Results:
- Morin administration prevented LPS-induced bone loss in mice.
- Morin significantly reduced osteoclast number and activity in vitro and in vivo.
- Morin inhibited the ROS/SHP1/c-Src signaling axis, crucial for osteoclast cytoskeletal organization.
Conclusions:
- Morin effectively protects against inflammatory bone loss by modulating osteoclast function.
- The protective effect is mediated through the disruption of the ROS/SHP1/c-Src pathway.
- Morin demonstrates significant therapeutic potential for treating inflammatory bone loss conditions.
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