Osteoimmunology: immunological mechanisms in pathogenesis of postmenopausal
Keywords:osteoporosis, menopause, estrogens, immunity
The most widespread form of osteoporosis is post-menopausal osteoporosis. Its main reason is estrogens defi ciency. However, the mechanisms of bone weight
loss at estrogens defi ciency are not limited to model of direct control actions of these hormones on bone tissue cells and are considerably more diffi cult. The data obtained are the evidence of interrelation between immune system and bone tissue and are of essential signifi cance for immune mechanisms in a pathogenesis of osteoporosis.
Last year’s scientifi c research showed that the dominant role in a regulation of osteoclasts diff erentiation and activation was given to the two cytokines – a
macrophage colony-stimulating factor and a receptor activator of nuclear factor kappa-B ligand (RANKL). In addition, for osteoclasts activity directly depends on
the production of several cytokines (TNF, IL-1, IL-6), which are called proosteoclastogenous cytokines.
At that, estrogen is capable to suppress RANKL, TNF, IL-1 and IL-6 by the direct eff ect on T-cells, indirectly – through an inhibition of IL-7 and stimulation of a
transforming growth factor beta – TGF-β.
It was showed, that estrogens defi ciency led to an increase of IL-17 production. This cytokine induces bone tissue loss by the increase of proosteoclastogenous
cytokines (TNF, IL-6 and RANKL) synthesis.
Thus, results of the recent research signifi cantly expanded our idea as to pathogenesis of post-menopausal osteoporosis. At present, on a cellular and molecular scale it is proved important and the dominant role of immune factors in the development of osteoporotic violations of bone tissue is likely to be caused by the estrogens defi ciency.
- Illovayskaya IA, Mikhailova DS, Repina EA The eff ect of estrogen on the functional state of the immune system women. Immunology. – 2011; 2. – P.109–112.
- Povoroznyuk VV, Grigorieva NV Menopause and Osteoporosis // Reproductive Endocrinology. – 2012; 2. – P.40–47.
- Asagiri M, Takayanagi H The molecular understanding of osteoclast diff erentiation // Bone. – 2007. – 2. – Р. 251–264.
- Bonds RS, Midoro-Horiuti T Estrogen eff ects in allergy and asthma // Curr. Opin. Allergy Clin. Immunol. – 2013. – 1. – Р. 92–99.
- Barlow DH, Bouchard P, Brandi ML et al. Bone fractures after menopause // Hum. Reprod. Update. – 2010. – 6. – Р. 761–773.
- Boyce BF, Xing L Biology of RANK, RANKL, and osteoprotegerin // Arthritis Res. Ther. – 2007. – 9 (1). – S. 1.
- Hanada R, Leibbrandt A, Hanada T et al. Central control of fever and female body temperature by RANKL/RANK // Nature. – 2009. – 462. – P. 505–509.
- Del Fattore A The tight relationship between osteoclasts and the immune system / A. Del Fattore, A.Teti // Infl amm. Allergy Drug Targets. – 2012. – 3. – Р. 181–187.
- Giannoni E, Guignard L, Reymond MK et al. Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns // Infect. Immun. – 2011. – 7. – Р. 2690–2698.
- D’Amelio P, Grimaldi A, Di Bella S et al. Estrogen defi ciency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis // Bone. – 2008. – 1. – Р. 92–100.
- Tyagi AM, Srivastava K, Mansoori MN et al. Estrogen defi ciency induces the diff erentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis // PLoS One. – 2012. – 7 (9). – Article e44552.
- Kanis JA, McCloskey EV, Johansson H et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women // Osteoporos Int. – 2013. – 1. – Р.23–57.
- Faienza MF, Ventura A, Cavallo L Postmenopausal Osteoporosis: The Role of Immune System Cells // Clinical and Developmental Immunology. – 2013. – Article ID 575936. – 6 p.
- Feng X, McDonald JM Disorders of bone remodeling // Annu. Rev. Pathol. – 2011. – 6. – 121–145.
- Geusens P, Lems WF Osteoimmunology and osteoporosis // Arthritis Res. Ther. – 2011. – 5. – 242.
- Aggarwal BB, Gupta SC, Kim JH Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey // Blood. – 2012. – 3. – Р.651–665.
- Breuil V, Ticchioni M, Testa J et al. Immune changes in post-menopausal osteoporosis: the Immunos study // Osteoporosis International. – 2010. – 5. – Р. 805–814.
- Kondoh S, Imai Y Estrogen actions on osteocytes // Clin. Calcium. – 2012. – 5. – Р. 721–726.
- Krum SA Direct transcriptional targets of sex steroid hormones in bone // J. Cell. Biochem. – 2011. – 2. – Р. 401–408.
- Kuroda Y, Matsuo K Molecular mechanisms of triggering, amplifying and targeting RANK signaling in osteoclasts // World J. Orthop. – 2012. – 11. – Р. 167–174.
- Lacativa PG, Farias ML Osteoporosis and infl ammation // Arq. Bras. Endocrinol. Metabol. – 2010. – 2. – Р. 123–132.
- Lundström W, Fewkes NM, Mackall CL IL-7 in human health and disease // Semin. Immunol. – 2012. – 3. – Р. 218–224.
- Lubberts E The role of IL-17 and family members in the pathogenesis of arthritis // Curr. Opin. Investig. Drugs. – 2003. – 5. – P. 572–577.
- Marie PJ, Kassem M Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation // The Journal of Clinical Endocrinology & Metabolism. – 2011. – 3. – Р. 600–609.
- Boyce BF, Yao Z, Xing L Osteoclasts have Multiple Roles in Bone in Addition to Bone Resorption // Crit. Rev. Eukaryot. Gene Expr. – 2009. – 3. – Р. 171–180.
- Wu Y, Humphrey MB, Nakamura MC Osteoclasts – the innate immune cells of the bone // Autoimmunity. – 2008. – 3. – Р. 183–194.
- Lee SH, Kim TS, Choi Y et al. Osteoimmunology: cytokines and the skeletal system // BMB Rep. – 2008. – 7. – Р.495–510.
- Lorenzo J, Horowitz M, Choi Y Osteoimmunology: interactions of the bone and immune system // Endocr. Rev. – 2008. – 4. – P. 403–440.
- Caetano-Lopes J, Canhão H, Fonseca JE Osteoimmunology – the hidden immune regulation of bone // Autoimmun Rev. – 2009. – 3. – P. 250–255.
- Rachner TD, Khosla S, Hofbauer LC Osteoporosis: now and the future // Lancet. – 2011. – 9. – Р. 1276–1287.
- Straub RH The complex role of estrogens in infl ammation // Endocr. Rev. – 2007. – 5. – Р. 521–574.
- Terpos E., Dimopoulos M.A. Interaction between the skeletal and immune systems in cancer: mechanisms and clinical implications // Cancer Immunol. Immunother. – 2011. – 3. – Р. 305–317.
- Mensah KA, Li J, Schwarz EM The emerging fi eld of osteoimmunology // Immunol. Res. – 2009. – 2-3. – Р. 100–113.
- Martin-Millan M, Almeida M, Ambrogini E et al. The estrogen receptor-alpha in osteoclasts mediates the protective eff ects of estrogens on cancellous but not cortical bone // Mol. Endocrinol. – 2010. – 2. – Р. 323–334.
- Paradowska A, Maślińiski W, Grzybowska-Kowalczyk A et al. The function of interleukin 17 in the pathogenesis of rheumatoid arthritis // Arch. Immunol. Ther. Exp. (Warsz). – 2007. – 5. – Р. 329–334.
- Thomas T New actors in bone remodelling: a role for the immune system // Bull. Acad. Natl. Med. – 2010. – 8. – Р. 1493–1504.
- Wong BR, Josien R, Lee SY et al. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specifi c survival factor // J. Exp. Med. – 1997. – 12. – Р. 2075–2080.
- Weitzmann MN, Pacifi ci R Estrogen defi ciency and bone loss: an infl ammatory tale // J. Clin. Invest. – 2006. – 5. – Р. 1186–1194.
- Zhao R Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective // Int. J. Med. Sci. – 2012. – 9. – Р. 825–832.
How to Cite
Copyright (c) 2014 В. В. Поворознюк, Н. А. Резниченко, Э. А. Майлян
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.