Lumichrome inhibits osteoclastogenesis and bone resorption through suppressing RANKL-induced NFAT activation and calcium signaling

Chuan Liu, Zhen Cao, Wen Zhang, Jennifer Tickner, Heng Qiu, Chao Wang, Kai Chen, Ziyi Wang, Renxiang Tan, Shiwu Dong, Jiake Xu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation. In this study, we found that lumichrome, a photodegradation product of riboflavin, inhibits RANKL-induced osteoclastogenesis and bone resorption as determined by tartrate-resistant acid phosphatase staining, immunofluorescence, reverse transcription-polymerase chain reaction, and western blot. Our results showed that lumichrome represses the expression of osteoclast marker genes, including cathepsin K (Ctsk) and Nfatc1. In addition, lumichrome suppressed RANKL-induced calcium oscillations, NFATc1, NF-κB, and MAPK signaling activation. Moreover, lumichrome promoted osteoblast differentiation at an early stage, as demonstrated by upregulated expression of osteoblast marker genes Alp, Runx2, and Col1a1. We also found that lumichrome reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis. In summary, our data suggest the potential of lumichrome as a therapeutic drug for osteolytic diseases.

Original languageEnglish
Pages (from-to)8971-8983
Number of pages13
JournalJournal of Cellular Physiology
Volume233
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018

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Calcium Signaling
Bone Resorption
Osteogenesis
Bone
Chemical activation
Calcium
Bone and Bones
Osteoclasts
Osteoblasts
Cathepsin K
RANK Ligand
Osteocytes
Riboflavin
Photolysis
Bone Diseases
Cytoplasmic and Nuclear Receptors
Genes
Osteoporosis
Reverse Transcription
Fluorescent Antibody Technique

Cite this

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title = "Lumichrome inhibits osteoclastogenesis and bone resorption through suppressing RANKL-induced NFAT activation and calcium signaling",
abstract = "The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation. In this study, we found that lumichrome, a photodegradation product of riboflavin, inhibits RANKL-induced osteoclastogenesis and bone resorption as determined by tartrate-resistant acid phosphatase staining, immunofluorescence, reverse transcription-polymerase chain reaction, and western blot. Our results showed that lumichrome represses the expression of osteoclast marker genes, including cathepsin K (Ctsk) and Nfatc1. In addition, lumichrome suppressed RANKL-induced calcium oscillations, NFATc1, NF-κB, and MAPK signaling activation. Moreover, lumichrome promoted osteoblast differentiation at an early stage, as demonstrated by upregulated expression of osteoblast marker genes Alp, Runx2, and Col1a1. We also found that lumichrome reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis. In summary, our data suggest the potential of lumichrome as a therapeutic drug for osteolytic diseases.",
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Lumichrome inhibits osteoclastogenesis and bone resorption through suppressing RANKL-induced NFAT activation and calcium signaling. / Liu, Chuan; Cao, Zhen; Zhang, Wen; Tickner, Jennifer; Qiu, Heng; Wang, Chao; Chen, Kai; Wang, Ziyi; Tan, Renxiang; Dong, Shiwu; Xu, Jiake.

In: Journal of Cellular Physiology, Vol. 233, No. 11, 01.11.2018, p. 8971-8983.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lumichrome inhibits osteoclastogenesis and bone resorption through suppressing RANKL-induced NFAT activation and calcium signaling

AU - Liu, Chuan

AU - Cao, Zhen

AU - Zhang, Wen

AU - Tickner, Jennifer

AU - Qiu, Heng

AU - Wang, Chao

AU - Chen, Kai

AU - Wang, Ziyi

AU - Tan, Renxiang

AU - Dong, Shiwu

AU - Xu, Jiake

PY - 2018/11/1

Y1 - 2018/11/1

N2 - The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation. In this study, we found that lumichrome, a photodegradation product of riboflavin, inhibits RANKL-induced osteoclastogenesis and bone resorption as determined by tartrate-resistant acid phosphatase staining, immunofluorescence, reverse transcription-polymerase chain reaction, and western blot. Our results showed that lumichrome represses the expression of osteoclast marker genes, including cathepsin K (Ctsk) and Nfatc1. In addition, lumichrome suppressed RANKL-induced calcium oscillations, NFATc1, NF-κB, and MAPK signaling activation. Moreover, lumichrome promoted osteoblast differentiation at an early stage, as demonstrated by upregulated expression of osteoblast marker genes Alp, Runx2, and Col1a1. We also found that lumichrome reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis. In summary, our data suggest the potential of lumichrome as a therapeutic drug for osteolytic diseases.

AB - The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation. In this study, we found that lumichrome, a photodegradation product of riboflavin, inhibits RANKL-induced osteoclastogenesis and bone resorption as determined by tartrate-resistant acid phosphatase staining, immunofluorescence, reverse transcription-polymerase chain reaction, and western blot. Our results showed that lumichrome represses the expression of osteoclast marker genes, including cathepsin K (Ctsk) and Nfatc1. In addition, lumichrome suppressed RANKL-induced calcium oscillations, NFATc1, NF-κB, and MAPK signaling activation. Moreover, lumichrome promoted osteoblast differentiation at an early stage, as demonstrated by upregulated expression of osteoblast marker genes Alp, Runx2, and Col1a1. We also found that lumichrome reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis. In summary, our data suggest the potential of lumichrome as a therapeutic drug for osteolytic diseases.

KW - calcium signaling

KW - lumichrome

KW - osteoclast

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