An osteocyte is a type of bone cell that is shaped like a flattened sphere and has branch-like structures. It is the most common cell in mature bone and can live as long as the organism itself. The adult human body contains about 42 billion osteocytes. These cells do not divide and have an average lifespan of 25 years. They are formed from osteoprogenitor cells, some of which become active osteoblasts (which may later become osteocytes). Osteoblasts and osteocytes develop from mesenchyme.
In mature bones, osteocytes and their branch-like structures are located inside spaces called lacunae (Latin for "pit") and canaliculi, respectively. Osteocytes are osteoblasts that become trapped in the bone material they create. They are connected to each other through long extensions of their cell bodies that travel through tiny canals called canaliculi. These canals allow the exchange of nutrients and waste through structures called gap junctions.
Although osteocytes have reduced ability to produce new materials and cannot divide, they play an important role in maintaining the bone matrix through mechanisms that sense mechanical forces. They help break down bone through a quick, temporary process called osteocytic osteolysis. Minerals such as hydroxyapatite, calcium carbonate, and calcium phosphate are deposited around the cell.
Structure
Osteocytes have a star-shaped form, about 7 micrometers deep and wide, and 15 micrometers long. The cell body varies in size from 5 to 20 micrometers in diameter and has 40 to 60 cell processes per cell, with a distance of 20 to 30 micrometers between cells. A mature osteocyte contains one nucleus located near the blood vessels, which has one or two nucleoli and a membrane. The cell has smaller amounts of endoplasmic reticulum, Golgi apparatus, and mitochondria compared to other cells. Cell processes extend outward toward the surfaces of bone in layers called circumferential lamellae, or toward a haversian canal and outer cement line in osteons of concentric lamellar bone. Osteocytes create a network of tiny spaces and channels within the hardened collagen matrix of bone. The cell bodies are found in spaces called lacunae, while the cell processes travel through narrow channels called canaliculi.
Development
The fossil record shows that osteocytes, which are special cells in bones, were found in jawless fish that lived between 400 and 250 million years ago. The size of osteocytes has been shown to change together with the size of an organism’s genome. Scientists use this relationship to study ancient genomes.
When bones form, an osteoblast, which is a type of bone-building cell, becomes trapped inside the bone matrix and turns into an "osteoid osteocyte." This cell stays connected to other osteoblasts through long, thread-like structures. Recent research suggests that vascular smooth muscle cells help osteocytes develop, but many details about how osteocytes form are still not fully understood. Several molecules are involved in this process, including matrix metalloproteinases (MMPs), dentin matrix protein 1 (DMP-1), osteoblast/osteocyte factor 45 (OF45), Klotho, TGF-beta inducible factor (TIEG), lysophosphatidic acid (LPA), E11 antigen, and oxygen. About 10 to 20% of osteoblasts become osteocytes. Osteoblasts that will turn into osteocytes slow down their production of bone matrix and are then surrounded by other osteoblasts that continue building the matrix.
Palumbo et al. (1990) identified three types of cells during the transition from osteoblasts to mature osteocytes: type I preosteocyte (osteoblastic osteocyte), type II preosteocyte (osteoid osteocyte), and type III preosteocyte (partially surrounded by mineral matrix). The "osteoid-osteocyte" must perform two tasks at the same time: control the hardening of bone and create branch-like structures that connect other cells. This process requires breaking down collagen and other molecules in the bone matrix. The change from a moving osteoblast to a trapped osteocyte takes about three days. During this time, the cell produces three times more extracellular matrix than its own volume, which causes the mature osteocyte’s body to shrink to 70% of the original osteoblast’s size. The cell changes shape from a polygonal form to one with long, branch-like structures that extend toward the area where bone hardens, and then to the vascular space or bone surface. As osteoblasts become osteocytes, the amount of alkaline phosphatase decreases, while casein kinase II and osteocalcin increase.
Osteocytes have high levels of proteins that help them survive in low-oxygen conditions. This may be because they are embedded deep within bones and receive limited oxygen. The amount of oxygen available might influence how osteoblasts turn into osteocytes. Additionally, low oxygen levels in osteocytes might contribute to bone loss caused by lack of use.
Function
Osteocytes are cells that do not actively move or change much, but they can create and change molecules, and send signals over long distances, similar to how the nervous system works. They are the most common type of cell in bone, with about 31,900 in each cubic millimeter of bovine bone and up to 93,200 in each cubic millimeter of rat bone. Many of the receptors that help bones function are found in mature osteocytes.
Osteocytes help control the amount of bone in the body. They have glutamate transporters that produce nerve growth factors after a bone breaks, showing they can sense changes and send messages. When osteocytes were destroyed in experiments, bones showed more breakdown, less new bone formation, loss of trabecular bone, and a reduced response to unloading.
Osteocytes act as sensors that detect mechanical forces and control the activity of osteoblasts and osteoclasts within a basic multicellular unit (BMU), a temporary structure where bone remodeling happens. Osteocytes send an inhibitory signal through their cell processes to osteoblasts, helping to recruit them for bone formation.
Osteocytes also play a key role in regulating the metabolism of minerals like phosphates. Specific proteins in osteocytes, such as sclerostin, help control mineral metabolism. Other molecules, including PHEX, DMP-1, MEPE, and FGF-23, are highly produced by osteocytes and regulate phosphate levels and biomineralization. Osteocyte activity is linked to diseases. For example, Lynda Bonewald found that osteocytes produce FGF23, which travels through the blood to signal the kidneys to release phosphorus. Low phosphorus levels can cause bones and teeth to soften and muscles to weaken, as seen in X-linked hypophosphatemia.
Osteocytes make sclerostin, a protein that stops bone formation by attaching to LRP5/LRP6 coreceptors and reducing Wnt signaling. Sclerostin, made by the SOST gene, is the first known way osteocytes communicate with osteoblasts and osteoclasts, which is important for bone remodeling. Only osteocytes produce sclerostin, which sends signals to nearby cells to stop bone formation. Sclerostin is reduced by parathyroid hormone (PTH) and mechanical loading. Sclerostin also blocks the activity of BMP, a protein that helps form bone and cartilage.
Pathophysiology
Osteonecrosis is a condition where bone cells die, leading to changes in bone growth and breakdown. Osteocyte necrosis begins with the death of blood cell-producing and fat cells in the bone marrow, causing swelling in the marrow. This process starts after 2 to 3 hours without oxygen. Signs of dead bone cells become visible 24 to 72 hours after oxygen levels drop. The first sign is the shrinking of cell nuclei, then the spaces where bone cells live become empty. New blood vessels form around the dead area, and increased blood flow begins. The repair process includes both breaking down and rebuilding bone, but not all dead bone is replaced. New bone grows over the dead parts, while some dead bone is broken down. More bone is broken down than rebuilt, leading to weakened bone structure, misshapen joints, and fractures under the cartilage.
Clinical significance
Important research has been conducted on a laboratory model that creates 3D structures to study how human CD34+ stem cells can become osteocytes, which are specialized bone cells. The findings show that these stem cells have the unique ability to develop into bone-forming cells and can help repair damaged bone early in the process. Osteocytes can die due to aging, physical damage, programmed cell death, or being consumed by osteoclasts, which are cells that break down bone. The number of dead osteocytes in bone increases with age, rising from less than 1% at birth to 75% after age 80. Osteocyte death through programmed cell death may be linked to reduced ability to respond to physical forces, which could lead to osteoporosis. When osteocytes die, they release substances that signal osteoclasts to break down bone.
Applying mechanical force, such as pressure or movement, helps osteocytes stay alive in laboratory settings and improves the flow of nutrients and oxygen through the tiny channels in bone, which supports their health. When bones are not used, such as during long periods of bed rest, osteocytes may experience low oxygen levels, leading to their death and triggering osteoclasts to break down bone. Repeated stress on bones can cause tiny cracks, which are often linked to osteocyte death through programmed cell death. These dead osteocytes may send signals to direct osteoclasts to repair damaged areas. Under normal conditions, osteocytes produce a substance called TGF-β, which prevents excessive bone breakdown. However, as bones age, TGF-β production decreases, while substances that encourage bone breakdown, such as RANKL and M-CSF, increase, leading to more bone loss.
When osteocytes are stimulated by mechanical forces, they release molecules like PGE2 and ATP, which help maintain the balance between bone formation and breakdown. Osteocyte death is associated with conditions like osteoporosis and osteoarthritis, which weaken bones and reduce the ability to detect and repair damage. Lack of oxygen, caused by immobility, certain medications, or oxygen removal, can also lead to osteocyte death. It is now understood that osteocytes react in various ways to materials used in medical implants.