Osteoimmunology

Osteoimmunology (όστέον, osteon from Greek, “bone”; immunitas from Latin, “immunity”; and λόγος, logos, from Greek “study”) is a field that emerged about 40 years ago that studies the interface between the skeletal system and the immune system,[1][2] comprising the “osteo-immune system”.[3][4] Osteoimmunology also studies the shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Over the past decade, osteoimmunology has been investigated clinically for the treatment of bone metastases, rheumatoid arthritis (RA), osteoporosis, osteopetrosis, and periodontitis. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.[5]

System similarities

The RANKL-RANK-OPG (osteoprotegerin) axis is an example of an important signaling system functioning both in bone[6] and immune cell communication. RANKL is expressed on osteoblasts and activated T cells, whereas RANK is expressed on osteoclasts, and dendritic cells (DCs), both of which can be derived from myeloid progenitor cells. Surface RANKL on osteoblasts as well as secreted RANKL provide necessary signals for osteoclast precursors to differentiate into osteoclasts. RANKL expression on activated T cells leads to DC activation through binding to RANK expressed on DCs. OPG, produced by DCs, is a soluble decoy receptor for RANKL that competitively inhibits RANKL binding to RANK.[7]

Crosstalk

The bone marrow cavity is important for the proper development of the immune system, and houses important stem cells for maintenance of the immune system. Within this space, as well as outside of it, cytokines produced by immune cells also have important effects on regulating bone homeostasis. Some important cytokines that are produced by the immune system, including RANKL, M-CSF, TNFa, ILs, and IFNs, affect the differentiation and activity of osteoclasts and bone resorption.[8] Such inflammatory osteoclastogenesis and osteoclast activation can be seen in ex vivo primary cultures of cells from the inflamed synovial fluid of patients with disease flare of the autoimmune disease rheumatoid arthritis.[9]

Clinical osteoimmunology

Clinical osteoimmunology is a field that studies a treatment or prevention of the bone related diseases caused by disorders of the immune system. Aberrant and/or prolonged activation of immune system leads to derangement of bone modeling and remodeling. Common diseases caused by disorder of osteoimmune system is osteoporosis and bone destruction accompanied by RA characterized by high infiltration of CD4+ T cells in rheumatoid joints, in which two mechanisms are involved: One is an indirect effect on osteoclastogenesis from rheumatoid synovial cells in joints since synovial cells have osteoclast precursors and osteoclast supporting cells, synovial macrophages are highly differentiated into osteoclasts with help of RANKL released from osteoclast supporting cells.[10][11] The second is an indirect effect on osteoclast differentiation and activity by the secretion of inflammatory cytokines such as IL-1, IL-6, TNFa, in synovium of RA, which increase RANKL signaling and finally bone destruction. A clinical approach to prevent bone related diseases caused by RA is OPG and RANKL treatment in arthritis. There is some evidence that infections (e.g. respiratory virus infection) can reduce the numbers of osteoblasts in bone, the key cells involved in bone formation.[12]

See also

References

  1. ↑ Arron JR, Choi Y (November 2000). "Bone versus immune system". Nature. 408 (6812): 535–6. doi:10.1038/35046196. PMID 11117729. S2CID 32822431.
  2. ↑ Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J, Choi Y (2006). "Osteoimmunology: interplay between the immune system and bone metabolism". Annual Review of Immunology. 24: 33–63. doi:10.1146/annurev.immunol.24.021605.090646. PMID 16551243.
  3. ↑ Lorenzo J, Horowitz M, Choi Y (June 2008). "Osteoimmunology: interactions of the bone and immune system". Endocrine Reviews. 29 (4): 403–40. doi:10.1210/er.2007-0038. PMC 2528852. PMID 18451259.
  4. ↑ Lorenzo J, Choi Y (December 2005). "Osteoimmunology". Immunological Reviews. 208: 5–6. doi:10.1111/j.0105-2896.2005.00340.x. PMID 16313336. S2CID 221814630.
  5. ↑ McHugh KP (April 2008). "Osteoimmunology in skeletal cell biology and disease". Autoimmunity. 41 (3): 181–2. doi:10.1080/08916930701694808. PMID 18365830. S2CID 22159566.
  6. ↑ Zaidi M (July 2007). "Skeletal remodeling in health and disease". Nature Medicine. 13 (7): 791–801. doi:10.1038/nm1593. PMID 17618270. S2CID 26486528.
  7. ↑ Theill LE, Boyle WJ, Penninger JM (2002). "RANK-L and RANK: T cells, bone loss, and mammalian evolution". Annual Review of Immunology. 20: 795–823. doi:10.1146/annurev.immunol.20.100301.064753. PMID 11861618.
  8. ↑ McInnes IB, Schett G (June 2007). "Cytokines in the pathogenesis of rheumatoid arthritis". Nature Reviews. Immunology. 7 (6): 429–42. doi:10.1038/nri2094. PMID 17525752. S2CID 28125222.
  9. ↑ Greisen SR, Einarsson HB, Hvid M, Hauge EM, Deleuran B, Kragstrup TW (September 2015). "Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis". APMIS. 123 (9): 779–86. doi:10.1111/apm.12416. PMID 26121915. S2CID 46022441.
  10. ↑ Takayanagi H, Oda H, Yamamoto S, Kawaguchi H, Tanaka S, Nishikawa T, Koshihara Y (November 1997). "A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis". Biochemical and Biophysical Research Communications. 240 (2): 279–86. doi:10.1006/bbrc.1997.7404. PMID 9388467.
  11. ↑ Takayanagi H (April 2007). "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems". Nature Reviews. Immunology. 7 (4): 292–304. doi:10.1038/nri2062. PMID 17380158. S2CID 25695543.
  12. ↑ Maltby S, Lochrin AJ, Bartlett B, Tay HL, Weaver J, Poulton IJ, et al. (January 2018). "Osteoblasts Are Rapidly Ablated by Virus-Induced Systemic Inflammation following Lymphocytic Choriomeningitis Virus or Pneumonia Virus of Mice Infection in Mice". Journal of Immunology. 200 (2): 632–642. doi:10.4049/jimmunol.1700927. PMC 5760340. PMID 29212906.
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