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 language | English |
|---|---|
| Pages (from-to) | 757-760 |
| Number of pages | 4 |
| Journal | Medical Hypotheses |
| Volume | 79 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2012 Dec 1 |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
Combined therapeutic application of mTOR inhibitor and vitamin D3 for inflammatory bone destruction of rheumatoid arthritis. / Kim, Tae Hwan; Choi, Sungjae; Lee, Young Ho; Song, Gwan Gyu; Ji, Jong Dae.
In: Medical Hypotheses, Vol. 79, No. 6, 01.12.2012, p. 757-760.Research output: Contribution to journal › Article
}
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 -