Osteoimmunology is the study of the interface between the skeletal system
The skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...

 and the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

, comprising the “osteo-immune system”. It is also the study of shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Some medical conditions in which this field is particularly relevant are bone metastases
Bone tumor
A bone tumor refers to a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign or malignant .-Classification:...

, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

, osteopetrosis
Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schonberg disease is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle,...

, and periodontitis. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.

System similarities

Receptor activator of nuclear factor kappa-B ligand , also known as tumor necrosis factor ligand superfamily member 11 , TNF-related activation-induced cytokine , osteoprotegerin ligand , and osteoclast differentiation factor , is a protein that in humans is encoded by the TNFSF11 gene.RANKL is...

Receptor Activator of Nuclear Factor κ B , also known as TRANCE Receptor, is a type I membrane protein that is expressed on the surface of osteoclasts and is involved in their activation upon ligand binding...

Osteoprotegerin , also known as osteoclastogenesis inhibitory factor , or tumor necrosis factor receptor superfamily member 11B , is a protein that in humans is encoded by the TNFRSF11B gene...

) axis is an example of an important signaling system functioning both in bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

 and immune cell communication. RANKL is expressed on osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...

s and activated T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s, whereas RANK is expressed on osteoclast
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone . This process is known as bone resorption. Osteoclasts were discovered by Kolliker in 1873...

s, and dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s (DCs), both of which can be derived from myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...

 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.


The bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 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, cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s 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
Macrophage colony-stimulating factor
Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. Eukaryotic cells also produce M-CSF in order to combat intercellular viral infection. M-CSF binds to the Colony...

, TNFa, IL
Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

s, and IFN
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...

s, affect the differentiation and activity of osteoclasts and bone resorption
Bone resorption
Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood....

. During chronic inflammation, the balance of bone modeling and remodeling can be greatly affected, contributing to painful and/or visible disorders in bone metabolism.
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