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

Identifieur interne : 000115 ( Main/Exploration ); précédent : 000114; suivant : 000116

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

Auteurs : Hyun-Jung Park [Corée du Sud] ; Malihatosadat Gholam-Zadeh [Corée du Sud] ; Jae-Hee Suh [Corée du Sud] ; Hye-Seon Choi [Corée du Sud]

Source :

RBID : pubmed:31687088

Descripteurs français

English descriptors

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.

DOI: 10.1155/2019/8982147
PubMed: 31687088
PubMed Central: PMC6800915


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Le document en format XML

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<term>Animals (MeSH)</term>
<term>Autophagy (drug effects)</term>
<term>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (metabolism)</term>
<term>Bone Resorption (chemically induced)</term>
<term>Bone Resorption (drug therapy)</term>
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<term>Cell Nucleus (drug effects)</term>
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<term>Osteoclasts (drug effects)</term>
<term>Osteoclasts (metabolism)</term>
<term>Osteoclasts (pathology)</term>
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<term>Phenanthridines (pharmacology)</term>
<term>Phenanthridines (therapeutic use)</term>
<term>Protective Agents (pharmacology)</term>
<term>Protective Agents (therapeutic use)</term>
<term>Protein Transport (drug effects)</term>
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<term>Résorption osseuse (induit chimiquement)</term>
<term>Résorption osseuse (traitement médicamenteux)</term>
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<div type="abstract" xml:lang="en">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 (
<i>μ</i>
CT) analysis revealed that lycorine attenuated LPS-induced bone loss in mice.
<i>In vivo</i>
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.
<i>In vitro</i>
, 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.</div>
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<AbstractText>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 (
<i>μ</i>
CT) analysis revealed that lycorine attenuated LPS-induced bone loss in mice.
<i>In vivo</i>
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.
<i>In vitro</i>
, 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.</AbstractText>
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