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An osteocyte, an oblate shaped type of
bone cell An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and ...
with dendritic processes, is the most commonly found
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active
osteoblasts Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functi ...
(which may further differentiate to osteocytes). Osteoblasts/osteocytes develop in
mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...
. In mature bones, osteocytes and their processes reside inside spaces called lacunae (
Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...
for a ''pit'') and canaliculi, respectively. Osteocytes are simply osteoblasts trapped in the matrix that they secrete. They are networked to each other via long cytoplasmic extensions that occupy tiny canals called canaliculi, which are used for exchange of nutrients and waste through
gap junctions Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regula ...
. Although osteocytes have reduced synthetic activity and (like osteoblasts) are not capable of mitotic division, they are actively involved in the routine turnover of bony matrix, through various mechanosensory mechanisms. They destroy bone through a rapid, transient (relative to
osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
s) mechanism called osteocytic
osteolysis Osteolysis is an active resorption of bone matrix by osteoclasts and can be interpreted as the reverse of ossification. Although osteoclasts are active during the natural formation of healthy bone the term "osteolysis" specifically refers to a pa ...
.
Hydroxyapatite Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. ...
, calcium carbonate and calcium phosphate is deposited around the cell.


Structure

Osteocytes have a stellate shape, approximately 7 micrometers deep and wide by 15 micrometers in length. The cell body varies in size from 5-20 micrometers in diameter and contain 40-60 cell processes per cell, with a cell to cell distance between 20-30 micrometers. A mature osteocyte contains a single nucleus that is located toward the vascular side and has one or two nucleoli and a membrane. The cell also exhibits a reduced size endoplasmic reticulum, Golgi apparatus and mitochondria, and cell processes that radiate largely towards the bone surfaces in circumferential lamellae, or towards a haversian canal and outer cement line typical of osteons in concentric lamellar bone. Osteocytes form an extensive lacunocanalicular network within the mineralized collagen type I matrix, with cell bodies residing within lacunae, and cell/dendritic processes within channels called canaliculi.


Development

The fossil record shows that osteocytes were present in bones of jawless fish 400 to 250 million years ago. Osteocyte size has been shown to covary with genome size; and this relationship has been used in paleogenomic research. During bone formation, an
osteoblast Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
is left behind and buried in the bone matrix as an "osteoid osteocyte", which maintains contact with other osteoblasts through extended cellular processes. The process of osteocytogenesis is largely unknown, but the following molecules have been shown to play a crucial role in the production of healthy osteocytes, either in correct numbers or specific distributions: matrix metalloproteinases (MMPs), dentin matrix protein 1 (DMP-1), osteoblast/osteocyte factor 45 (OF45), Klotho, TGF-beta inducible factor (TIEG),
lysophosphatidic acid Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule. Function LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (als ...
(LPA), E11 antigen, and oxygen. 10–20% of osteoblasts differentiate into osteocytes. Those osteoblasts on the bone surface that are destined for burial as osteocytes slow down matrix production, and are buried by neighboring osteoblasts that continue to produce matrix actively. Palumbo et al. (1990) distinguish three cell types from osteoblast to mature osteocyte: type I preosteocyte (osteoblastic osteocyte), type II preosteocyte (osteoid osteocyte), and type III preosteocyte (partially surrounded by mineral matrix). The embedded "osteoid-osteocyte" must do two functions simultaneously: regulate mineralization and form connective dendritic processes, which requires cleavage of collagen and other matrix molecules. The transformation from motile osteoblast to entrapped osteocyte takes about three days, and during this time, the cell produces a volume of extracellular matrix three times its own cellular volume, which results in 70% volume reduction in the mature osteocyte cell body compared to the original osteoblast volume. The cell undergoes a dramatic transformation from a polygonal shape to a cell that extends dendrites toward the mineralizing front, followed by dendrites that extend to either the vascular space or bone surface. As the osteoblast transitions to an osteocyte, alkaline phosphatase is reduced, and casein kinase II is elevated, as is
osteocalcin Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein. Because osteocalcin has g ...
. Osteocytes appear to be enriched in proteins that are resistant to hypoxia, which appears to be due to their embedded location and restricted oxygen supply. Oxygen tension may regulate the differentiation of osteoblasts into osteocytes, and osteocyte hypoxia may play a role in disuse-mediated bone resorption.


Function

Although osteocytes are relatively inert cells, they are capable of molecular synthesis and modification, as well as transmission of signals over long distances, in a way similar to the nervous system. They are the most common cell type in bone (31,900 per cubic millimeter in bovine bone to 93,200 per cubic millimeter in rat bone). Most of the receptor activities that play an important role in bone function are present in the mature osteocyte. Osteocytes are an important regulator of bone mass. Osteocytes contain glutamate transporters that produce nerve growth factors after bone fracture, evidence of a sensing and information transfer system. When osteocytes were experimentally destroyed, the bones showed a significant increase in bone resorption, decreased bone formation, trabecular bone loss, and loss of response to unloading. Osteocytes are mechanosensor cells that control the activity of
osteoblasts Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts functi ...
and osteoclasts within a basic multicellular unit (BMU), a temporary anatomic structure where bone remodeling occurs. Osteocytes generate an inhibitory signal that is passed through their cell processes to osteoblasts for recruitment to enable bone formation. Osteocytes are also a key endocrine regulator in the metabolism of minerals such as phosphates. Osteocyte-specific proteins such as sclerostin have been shown to function in mineral metabolism, as well as other molecules such as PHEX, DMP-1,
MEPE Matrix extracellular phosphoglycoprotein (Osteoblast/osteocyte factor 45) is a protein that in humans is encoded by the ''MEPE'' gene. A conserved RGD motif is found in this protein, and this is potentially involved in integrin recognition. ...
, and FGF-23, which are highly expressed by osteocytes and regulate phosphate and biomineralization. Osteocyte regulation can be linked to disease. For example,
Lynda Bonewald Lynda Bonewald is a professor of anatomy, cell biology, physiology, and orthopaedic surgery and the founding director of the Indiana Center for Musculoskeletal Health (ICMH) at the Indiana University School of Medicine. She studies bone and th ...
determined that osteocytes make FGF23, which travels through the bloodstream to trigger the release of phosphorus by the kidneys. Without enough phosphorus bones and teeth soften, and muscles become weak, as in
X-linked hypophosphatemia X-linked hypophosphatemia (XLH) is an X-linked dominant form of rickets (or osteomalacia) that differs from most cases of dietary deficiency rickets in that vitamin D supplementation does not cure it. It can cause bone deformity including short s ...
.


Sclerostin

Osteocytes synthesize
sclerostin Sclerostin is a protein that in humans is encoded by the ''SOST'' gene. Sclerostin is a secreted glycoprotein with a C-terminal cysteine knot-like (CTCK) domain and sequence similarity to the DAN (differential screening-selected gene aberrative ...
, a secreted protein that inhibits bone formation by binding to LRP5/LRP6 coreceptors and blunting Wnt signaling. Sclerostin, the product of the
SOST Sost or SOST may refer to: Places * Sost, Afghanistan, a village in Badakhshan Province *Sost, Pakistan Sost or Sust ( ur, ) is a village in Gojal, Upper Hunza, Gilgit–Baltistan, Pakistan. It is the last town inside Pakistan on the Karak ...
gene, is the first mediator of communication between osteocytes, bone forming osteoblasts and bone resorbing osteoclasts, critical for bone remodeling. Only osteocytes express sclerostin, which acts in a paracrine fashion to inhibit bone formation. Sclerostin is inhibited by parathyroid hormone (PTH) and mechanical loading. Sclerostin antagonizes the activity of BMP (bone morphogenetic protein), a cytokine that induces bone and cartilage formation.


Pathophysiology

Osteonecrosis refers to the classic pattern of cell death and complex osteogenesis and bone resorption processes. Osteocyte necrosis (ON) initiates with hematopoietic and adipocytic cellular necrosis along with interstitial marrow edema. ON happens after about 2 to 3 hours of anoxia; histological signs of osteocytic necrosis do not display until about 24 to 72 hours after hypoxia. ON is first characterized by pyknosis of nuclei, followed by hollow osteocyte lacunae. Capillary revascularization and reactive hyperemia slightly take place at the periphery of the necrosis site, followed by a repair process combining both bone resorption and production that incompletely changes dead with living bone. Nouveau bone overlays onto dead trabeculae along with fragmentary resorption of dead bone. Bone resorption outperforms formation resulting in a net removal of bone, deformed structural integrity of the subchondral trabeculae, joint incongruity, and subchondral fracture.


Clinical significance

Clinically important research of gel based ''in vitro'' 3D model for the osteocytic potentiality of human
CD34 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...
+ stem cells has been described. The results confirm that the human CD34+ stem cells possess unique osteogenic differentiation potential and can be used in the early regeneration of injured bone. Osteocytes die as a consequence of
senescence Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence invol ...
, degeneration/necrosis,
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
(programmed cell death), and/or osteoclastic engulfment. The percentage of dead osteocytes in bone increases with age from less than 1% at birth to 75% after age 80. Osteocyte apoptosis is thought to be related to decreased mechanotransduction, which possibly leads to the development of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...
. Apoptotic osteocytes release apoptotic bodies expressing RANKL to recruit osteoclasts. Mechanical loading increases osteocyte viability ''in vitro'', and contributes to solute transport through the lacuno-canalicular system in bone, which enhances oxygen and nutrient exchange and diffusion to osteocytes. Skeletal unloading has been shown to induce osteocyte hypoxia ''in vivo'', this is when osteocytes undergo apoptosis and recruit osteoclasts to resorb bone. Microdamage in bone occurs as the result of repetitive events of cycling loading, and appears to be associated with osteocyte death by apoptosis, which appear to secrete a signal to target osteoclasts to perform remodeling at a damaged site. Under normal conditions, osteocytes express high amounts of TGF-β and thus repress bone resorption, but when bone grows old, the expression levels of TGF-β decrease, and the expression of osteoclast-stimulatory factors, such as
RANKL Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiati ...
and M-CSF increases, bone resorption is then enhanced, leading to net bone loss. Mechanical stimulation of osteocytes results in opening of hemichannels to release PGE2 and ATP, among other biochemical signaling molecules, which play a crucial role in maintaining the balance between bone formation and resorption. Osteocyte cell death can occur in association with pathologic conditions such as osteoporosis and
osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the ...
, which leads to increased skeletal fragility, linked to the loss of ability to sense microdamage and/or signal repair. Oxygen deprivation that occurs as the result of immobilization (bed rest), glucocorticoid treatment, and withdrawal of oxygen have all been shown to promote osteocyte apoptosis. It is now recognized that osteocytes respond in a variety of ways to the presence of implant biomaterials.


See also

*
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corti ...


References


External links

* – "Cartilage and Bone and Bone Histogenesis: cells of* – "Cartilage and Bone and Bone Histogenesis: compact bone"* =
Histology at ou.edu
{{Authority control Skeletal system Secretory cells Human cells