Lycorine Attenuates Autophagy in Osteoclasts via an Axis of mROS/TRPML1/TFEB to Reduce LPS-Induced Bone Loss.

Hyun-Jung Park,Hye-Seon Choi,Jae-Hee Suh,Malihatosadat Gholam-Zadeh

doi:10.1155/2019/8982147

Hyun-Jung Park, Hye-Seon Choi + Show 2 more

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https://doi.org/10.1155/2019/8982147

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Abstract

Lycorine, a plant alkaloid, exhibits anti-inflammatory activity by acting in macrophages that share precursor cells with osteoclasts (OCs). We hypothesized that lycorine might decrease bone loss by acting in OCs after lipopolysaccharide (LPS) stimulation, since OCs play a main role in LPS-induced bone loss. Microcomputerized tomography (μCT) analysis revealed that lycorine attenuated LPS-induced bone loss in mice. In vivo tartrate-resistant acid phosphatase (TRAP) staining showed that increased surface area and number of OCs in LPS-treated mice were also decreased by lycorine treatment, suggesting that OCs are responsible for the bone-sparing effect of lycorine. In vitro, the increased number and activity of OCs induced by LPS were reduced by lycorine. Lycorine also decreased LPS-induced autophagy in OCs by evaluation of decreased lipidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3) (LC3II) and increased sequestosome 1 (p62). Lycorine attenuated oxidized transient receptor potential cation channel, mucolipin subfamily (TRPML1) by reducing mitochondrial reactive oxygen species (mROS) and decreased transcription factor EB (TFEB) nuclear translocation. Lycorine reduced the number and activity of OCs by decreasing autophagy in OCs via an axis of mROS/TRPML1/TFEB. Collectively, lycorine protected against LPS-induced bone loss by acting in OCs. Our data highlight the therapeutic potential of lycorine for protection against inflammatory bone loss.

Highlights

Inflammatory osteolysis is caused by the pathogenesis of infectious and inflammatory disease, resulting in irreversible bone erosion
A plant alkaloid purified from Lycoris radiata [9], protects mice from inflammatory bone loss induced by LPS
When lycorine was administered to LPS-injected mice, OC.N/BS, OC.S/BS, and serum CTX-1 levels were significantly reduced, whereas no changes were observed with in vivo bone formation markers, serum alkaline phosphatase (ALP) and osteocalcin, implying that lycorine decreases bone loss induced by LPS in mice through OCs

Summary

Introduction

Inflammatory osteolysis is caused by the pathogenesis of infectious and inflammatory disease, resulting in irreversible bone erosion. This bone loss has been reported to be due to inflammation that stimulates osteoclasts (OCs) either directly or indirectly by activating osteoblasts/stromal cells [1]. Injection of lipopolysaccharide (LPS) leads to increased eroded surface area by increasing the number of OCs in rat femurs [2]. LPS has been shown to increase the number and activity of OCs, leading to bone loss [3, 4]. Increased OC number by LPS has been reported to be due to the induction of differentiation via reactive oxygen species (ROS) [5] and enhancing OC survival [6, 7]. LPS-induced autophagy has been demonstrated to be responsible for increased OC formation and OC activity [4, 5, 8]

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