Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2
Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions....
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/18/6723 |
| _version_ | 1797553812193411072 |
|---|---|
| author | Chia-Hung Yen Chin-Mu Hsu Samuel Yien Hsiao Hui-Hua Hsiao |
| author_facet | Chia-Hung Yen Chin-Mu Hsu Samuel Yien Hsiao Hui-Hua Hsiao |
| author_sort | Chia-Hung Yen |
| collection | DOAJ |
| description | Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs. |
| first_indexed | 2024-03-10T16:21:59Z |
| format | Article |
| id | doaj.art-d6be080bae564860bb50bfb4f215a5d3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:21:59Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d6be080bae564860bb50bfb4f215a5d32023-11-20T13:39:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012118672310.3390/ijms21186723Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2Chia-Hung Yen0Chin-Mu Hsu1Samuel Yien Hsiao2Hui-Hua Hsiao3Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, TaiwanDivision of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of biology, University of Rutgers-Camden, Camden, NJ 08102, USACenter for Cancer Research, Kaohsiung Medical University, Kaohsiung 807, TaiwanOsteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs.https://www.mdpi.com/1422-0067/21/18/6723nuclear factor erythroid 2-related factor 2 (NRF2)osteoclastosteoclastogenesisosteoblastmultiple myelomathe receptor activator of NF-kappa B (RANK) |
| spellingShingle | Chia-Hung Yen Chin-Mu Hsu Samuel Yien Hsiao Hui-Hua Hsiao Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 International Journal of Molecular Sciences nuclear factor erythroid 2-related factor 2 (NRF2) osteoclast osteoclastogenesis osteoblast multiple myeloma the receptor activator of NF-kappa B (RANK) |
| title | Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 |
| title_full | Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 |
| title_fullStr | Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 |
| title_full_unstemmed | Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 |
| title_short | Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2 |
| title_sort | pathogenic mechanisms of myeloma bone disease and possible roles for nrf2 |
| topic | nuclear factor erythroid 2-related factor 2 (NRF2) osteoclast osteoclastogenesis osteoblast multiple myeloma the receptor activator of NF-kappa B (RANK) |
| url | https://www.mdpi.com/1422-0067/21/18/6723 |
| work_keys_str_mv | AT chiahungyen pathogenicmechanismsofmyelomabonediseaseandpossiblerolesfornrf2 AT chinmuhsu pathogenicmechanismsofmyelomabonediseaseandpossiblerolesfornrf2 AT samuelyienhsiao pathogenicmechanismsofmyelomabonediseaseandpossiblerolesfornrf2 AT huihuahsiao pathogenicmechanismsofmyelomabonediseaseandpossiblerolesfornrf2 |