Combined therapeutic application of mTOR inhibitor and vitamin D3 for inflammatory bone destruction of rheumatoid arthritis

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D3 modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D3 can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.

Original languageEnglish
Pages (from-to)757-760
Number of pages4
JournalMedical Hypotheses
Volume79
Issue number6
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

Cholecalciferol
Rheumatoid Arthritis
Bone and Bones
Osteoclasts
Phosphatidylinositol 3-Kinases
Therapeutics
Osteitis
Antirheumatic Agents
Critical Pathways
Poisons
Periodontitis
Giant Cells
Morbidity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{0321dc8969f0461299f47037554be030,
title = "Combined therapeutic application of mTOR inhibitor and vitamin D3 for inflammatory bone destruction of rheumatoid arthritis",
abstract = "Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D3 modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D3 can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.",
author = "Kim, {Tae Hwan} and Sungjae Choi and Lee, {Young Ho} and Song, {Gwan Gyu} and Ji, {Jong Dae}",
year = "2012",
month = "12",
day = "1",
doi = "10.1016/j.mehy.2012.08.022",
language = "English",
volume = "79",
pages = "757--760",
journal = "Medical Hypotheses",
issn = "0306-9877",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Combined therapeutic application of mTOR inhibitor and vitamin D3 for inflammatory bone destruction of rheumatoid arthritis

AU - Kim, Tae Hwan

AU - Choi, Sungjae

AU - Lee, Young Ho

AU - Song, Gwan Gyu

AU - Ji, Jong Dae

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D3 modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D3 can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.

AB - Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D3 modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D3 can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.

UR - http://www.scopus.com/inward/record.url?scp=84869079375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869079375&partnerID=8YFLogxK

U2 - 10.1016/j.mehy.2012.08.022

DO - 10.1016/j.mehy.2012.08.022

M3 - Article

VL - 79

SP - 757

EP - 760

JO - Medical Hypotheses

JF - Medical Hypotheses

SN - 0306-9877

IS - 6

ER -