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An osteoclast () is a type of bone cell that removes bone tissue. This function is critical in the maintenance, repair, and bone remodeling of of the vertebrate skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium.
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 cell membrane; this border is called ruffled border. The ruffled border lies in contact with the bone surface within a resorption bay. The periphery of the ruffled border is surrounded by a ring-like zone of cytoplasm, which is devoid of cell Organelle but rich in Microfilament. This zone is called the clear zone or sealing zone. The actin filaments enable the cell membrane surrounding the sealing zone to be anchored firmly to the bony wall of Howship's lacunae. In this way, a closed subosteoclastic compartment is created between the ruffled border and the bone that is undergoing resorption. The osteoclasts secrete Hydrogen ion, collagenase, cathepsin K and hydrolytic enzymes into this compartment. Resorption of bone matrix by the osteoclasts involves two steps: (1) dissolution of inorganic components (minerals), and (2) digestion of organic component of the bone matrix. The osteoclasts pump hydrogen ions into the subosteoclastic compartment and thus create an acidic microenvironment, which increases solubility of bone mineral, resulting in the release and re-entry of bone minerals into the cytoplasm of osteoclasts to be delivered to nearby capillaries. After the removal of minerals, collagenase and gelatinase are secreted into the subosteoclastic compartment. These enzymes digest and degrade collagen and other organic components of decalcified bone matrix. The degradation products are phagocytosed by osteoclasts at the ruffled border. Because of their phagocytic properties, osteoclasts are considered to be a component of the mononuclear phagocyte system (MPS). The activity of osteoclasts is controlled by hormones and cytokines. Calcitonin, a hormone of the thyroid gland, suppresses osteoclastic activity. Osteoclasts do not have receptors for parathyroid hormone (PTH). However, PTH stimulates osteoblasts to secrete a cytokine called osteoclast-stimulating factor, which is a potent stimulator of osteoclastic activity.Medical Histology by Laiq Hussain Siddiqui (6th Edition)
An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with the absorption of the roots of deciduous teeth.
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.
M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocyte/macrophage derived cells.
RANKL is a member of the tumour necrosis family (TNF), and is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1) through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs and is not upregulated. NFATc1 stimulation, however, begins ~24–48 hours after binding occurs and its expression has been shown to be RANKL dependent.
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.
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 reactive oxygen species generated by TRAP, further degrades the bone extracellular matrix.
Several other cathepsins are expressed in osteoclasts including cathepsin B, cathepsin C, cathepsin D, cathepsin E, cathepsin G, and L. The function of these cysteine and aspartic proteases is generally unknown within bone, and they are expressed at much lower levels than cathepsin K.
Studies on cathepsin L knockout mice have been mixed, with a report of reduced trabecular bone in homozygous and heterozygous cathepsin L knockout mice compared to wild-type and another report finding no skeletal abnormalities.
MMP9 is associated with the bone microenvironment. It is expressed by osteoclasts, and is known to be required for osteoclast cell migration and is a powerful gelatinase. Transgenic mice lacking MMP-9 develop defects in bone development, intraosseous angiogenesis, and fracture repair.
MMP-13 is believed to be involved in bone resorption and in osteoclast differentiation, as knockout mice revealed decreased osteoclast numbers, osteopetrosis, and decreased bone resorption.
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.
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. 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. This activity completes the bone resorption, and both the mineral components and collagen fragments are released to the general circulation.
Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANKL. These molecules also regulate differentiation of the osteoclast.
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.
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