Biology: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 axis (OPG stands for osteoprotegerin) 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][9] 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][10]
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.[11][12] 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.[13]
See also
- Bone metabolism
- Osteoimmunology and Osseointegration
- HSC
- Osteoarthritis
References
- ↑ "Bone versus immune system". Nature 408 (6812): 535–6. November 2000. doi:10.1038/35046196. PMID 11117729.
- ↑ "Osteoimmunology: interplay between the immune system and bone metabolism". Annual Review of Immunology 24: 33–63. 2006. doi:10.1146/annurev.immunol.24.021605.090646. PMID 16551243.
- ↑ "Osteoimmunology: interactions of the bone and immune system". Endocrine Reviews 29 (4): 403–40. June 2008. doi:10.1210/er.2007-0038. PMID 18451259.
- ↑ "Osteoimmunology". Immunological Reviews 208: 5–6. December 2005. doi:10.1111/j.0105-2896.2005.00340.x. PMID 16313336.
- ↑ "Osteoimmunology in skeletal cell biology and disease". Autoimmunity 41 (3): 181–2. April 2008. doi:10.1080/08916930701694808. PMID 18365830.
- ↑ "Skeletal remodeling in health and disease". Nature Medicine 13 (7): 791–801. July 2007. doi:10.1038/nm1593. PMID 17618270.
- ↑ "RANK-L and RANK: T cells, bone loss, and mammalian evolution". Annual Review of Immunology 20: 795–823. 2002. doi:10.1146/annurev.immunol.20.100301.064753. PMID 11861618.
- ↑ "Cytokines in the pathogenesis of rheumatoid arthritis". Nature Reviews. Immunology 7 (6): 429–42. June 2007. doi:10.1038/nri2094. PMID 17525752.
- ↑ 9.0 9.1 Shirazi, Sajjad; Ravindran, Sriram; Cooper, Lyndon F. (2022-11-09). "Topography-mediated immunomodulation in osseointegration; Ally or Enemy" (in en). Biomaterials 291: 121903. doi:10.1016/j.biomaterials.2022.121903. ISSN 0142-9612. PMID 36410109. PMC 10148651. https://www.sciencedirect.com/science/article/pii/S0142961222005439.
- ↑ "Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis". APMIS 123 (9): 779–86. September 2015. doi:10.1111/apm.12416. PMID 26121915.
- ↑ "A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis". Biochemical and Biophysical Research Communications 240 (2): 279–86. November 1997. doi:10.1006/bbrc.1997.7404. PMID 9388467.
- ↑ "Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems". Nature Reviews. Immunology 7 (4): 292–304. April 2007. doi:10.1038/nri2062. PMID 17380158.
- ↑ "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. January 2018. doi:10.4049/jimmunol.1700927. PMID 29212906.
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