Osteoclast
Osteoclast | |
---|---|
bone tissue | |
Identifiers | |
Latin | osteoclastus |
MeSH | D010010 |
TH | H2.00.03.7.00005 |
FMA | 66781 |
Anatomical terms of microanatomy] |
An osteoclast (from
Osteoclasts are found on those surfaces of bone that are undergoing resorption. On such surfaces, the osteoclasts are seen to be located in shallow depressions called resorption bays (Howship's lacunae). The resorption bays are created by the erosive action of osteoclasts on the underlying bone. The border of the lower part of an osteoclast exhibits finger-like processes due to the presence of deep infoldings of the
An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth.[2][3][4]
Structure
An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have four nuclei[5] and are 150–200 µm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate.[6][7] The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone.
Location
In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or
At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue. This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone.
Development
Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and
M-CSF acts through its receptor on the osteoclast, c-fms (
RANKL is a member of the tumour necrosis family (
Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. While osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells.[13][14]
Function
Once activated, osteoclasts move to areas of microfracture in the bone by
Cathepsin K and other cathepsins
Cathepsin K has an optimal enzymatic activity in acidic conditions. It is synthesized as a proenzyme with a molecular weight of 37kDa, and upon activation by autocatalytic cleavage, is transformed into the mature, active form with a molecular weight of ~27kDa.
Upon polarization of the osteoclast over the site of resorption, cathepsin K is secreted from the ruffled border into the resorptive pit. Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory domain. Within these intercellular vesicles, cathepsin K, along with
Several other cathepsins are expressed in osteoclasts including
Studies on cathepsin L
Matrix metalloproteinases
The
MMP9 is associated with the bone microenvironment. It is expressed by osteoclasts, and is known to be required for osteoclast migration and is a powerful gelatinase. Transgenic mice lacking MMP-9 develop defects in bone development, intraosseous angiogenesis, and fracture repair.
MMPs expressed by the osteoclast include MMP-9, -10, -12, and -14. apart from MMP-9, little is known about their relevance to the osteoclast, however, high levels of MMP-14 are found at the sealing zone.
Osteoclast physiology
In the 1980s and 90s the physiology of typical osteoclasts was studied in detail. With the isolation of the ruffled border, ion transport across it was studied directly in biochemical detail. Energy-dependent acid transport was verified and the postulated proton pump purified.[15][16] With the successful culture of osteoclasts, it became apparent that they are organized to support the massive transport of protons for acidification of the resorption compartment and solubilization of the bone mineral. This includes ruffled border Cl− permeability to control membrane potential and basolateral Cl−/HCO3− exchange to maintain cytosolic pH in physiologically acceptable ranges.[17][18][19]
The effectiveness of its ion secretion depends upon the osteoclast forming an effective seal around the resorption compartment. The positioning of this "sealing zone" appears to be mediated by integrins expressed on the osteoclast surface.[20] With the sealing zone in place, the multinucleated osteoclast reorganizes itself. Developing the highly invaginated ruffled membrane apposing the resorption compartment allows massive secretory activity. In addition, it permits the vesicular transcytosis of the mineral and degraded collagen from the ruffled border to the free membrane of the cell, and its release into the extracellular compartment.[21][22] This activity completes the bone resorption, and both the mineral components and collagen fragments are released to the general circulation.
Regulation
Osteoclasts are regulated by several
Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANK ligand. These molecules also regulate differentiation of the osteoclast.[24][25]
Odontoclast
An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth.[2][3][4]
Alternate use of term
An osteoclast can also be an instrument used to fracture and reset bones (the origin is Greek osteon: bone and klastos: broken). To avoid confusion, the cell was originally termed osotoclast. When the surgical instrument went out of use, the cell became known by its present name.
Clinical significance
Giant osteoclasts can occur in some diseases, including Paget's disease of bone and bisphosphonate toxicity.
In cats, abnormal odontoclast activity can cause feline odontoclastic resorptive lesions, necessitating extraction of the affected teeth.
Osteoclasts play a major role in orthodontic tooth movement and pathologic migration of periodontally compromised teeth.
History
Osteoclasts were discovered by Kölliker in 1873.[12]
See also
- List of human cell types derived from the germ layers
- List of distinct cell types in the adult human body
References
- ^ Medical Histology by Laiq Hussain Siddiqui (6th Edition)
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External links
- MedicineNet Archived 2013-05-25 at the Wayback Machine
- Osteoclasts at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- The Life of Osteoclast
- Random42: Animation by Random42 Scientific Communication on the role of osteoclasts in bone remodeling