Osteoclast and Its Role in Bone Resorption

If you are asked to explain what are Osteoclasts or Osteoclast meaning, then the answer will be — an osteoclast is a type of bone cell that breaks down bone tissue (from Ancient Greek (osteon) 'bone' and (clastos) 'broken'). The care, repair, and remodelling of vertebral skeleton bones rely on this feature.

Osteoclast Definition: Osteoclasts are multinucleated cells of the myeloid lineage that clear away mineralized and calcified constituents of the bone matrix that have become aged or weakened. They are 150-200m in diameter and have 2-12 nuclei (typically 5). They have high acid-phosphatase activity. 

Osteoclast Cells Structure

Osteoclast cells have two distinct features: a ruffled border and a sealing zone. The ruffled border is formed by the mixing of secretory lysosomes with the plasma membrane, resulting in a convoluted membrane. An actin filament ring surrounds the ruffled border in the sealing region, isolating the acidified microenvironment within the cell from the rest of the extracellular space.

An osteoclast is a large multinucleated cell with five nuclei and a diameter of 150–200 m. Human osteoclasts on bone have five nuclei and a diameter of 150–200 m. When osteoclast-inducing cytokines are used to transform macrophages to osteoclasts, very large cells with diameters of up to 100 m result. Because of the non-natural substrate, these cells can have thousands of nuclei and normally express major osteoclast proteins, but they differ significantly from cells in living bone. The multinucleated assembled osteoclast's size enables it to concentrate several macrophages' ion transfer, protein secretory, and vesicular transport capabilities on a small area of bone.

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Where are Osteoclast Cells Located?

Osteoclasts are present in resorption bays, also known as Howship's lacunae, which are pits in the surface of the bone. Osteoclasts have a cytoplasm that is homogeneous and "foamy" in colour. A high concentration of vesicles and vacuoles causes this appearance. Lysosomes containing acid phosphatase are found in these vacuoles. This allows osteoclasts to be identified by staining for high levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K. The rough endoplasmic reticulum of osteoclasts is sparse, but the Golgi complex is large.

The osteoclast forms a specialised cell membrane, the "ruffled border," that opposes the surface of the bone tissue at a site of active bone resorption. This morphologic feature of an osteoclast that is actively resorbing bone promotes bone removal by significantly raising the cell surface for secretion and uptake of the resorption compartment contents, and it is a morphologic feature of an osteoclast that is actively resorbing bone.

Osteoclast Function

Chemotaxis directs osteoclasts to areas of microfracture in the bone after they have been triggered. Osteoclasts live in Howship's lacunae, narrow cavities created by the digestion of the underlying bone. The sealing zone is where the plasma membrane of the osteoclast attaches to the underlying bone. Sealing zones are described by podosomes, which are specialised adhesion structures. Integrin receptors, such as v3, promote attachment to the bone matrix through the unique amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin.

Carbonic anhydrase (H2O + CO2 HCO3 + H+) releases hydrogen ions into the resorptive cavity through the ruffled boundary, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water, and other substances. Some types of osteopetrosis have been linked to a malfunction of the carbonic anhydrase enzyme. Proton pumps, precisely a special vacuolar-ATPase, pump hydrogen ions against a high concentration gradient. This enzyme has been studied to see if it will help prevent osteoporosis.

Several hydrolytic enzymes, including members of the cathepsin and matrix metalloprotease (MMP) families, are also released to digest the matrix's organic components. Lysosomes release these enzymes into the compartment. Cathepsin K is the most important of these hydrolytic enzymes.

What is Cathepsin K?

Cathepsin K is a collagenolytic, papain-like cysteine protease that is secreted into the resorptive pit and is primarily expressed in osteoclasts. The main protease involved in the degradation of type I collagen and other non-collagenous proteins is cathepsin K. Pycnodysostosis, a hereditary osteopetrotic disorder characterised by a lack of functional cathepsin K expression, is linked to mutations in the cathepsin K gene. Cathepsin K knockout mice develop an osteopetrotic phenotype, which is partly compensated for by increased expression of other proteases and enhanced osteoclastogenesis.

In acidic conditions, cathepsin K has the best enzymatic activity. It is synthesised as a 37kDa proenzyme that is transformed into a mature, active form with a molecular weight of 27kDa after activation by autocatalytic cleavage.

Cathepsin K is secreted from the ruffled border into the resorptive pit when the osteoclast is polarised over the resorption site. Intercellular vesicles transport cathepsin K across the ruffled boundary, where it is then released by the functional secretory domain. The bone extracellular matrix is further degraded by cathepsin K and reactive oxygen species produced by TRAP within these intercellular vesicles.

The cathepsins B, C, D, E, G, and L are among the cathepsins expressed in osteoclasts. These cysteine and aspartic proteases are expressed at far lower levels than cathepsin K, and their function is unknown within the bone.

Osteoblast vs Osteoclast

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What are Osteoblast Cells?

Osteoblasts are single-nucleated cells that synthesise bone. Osteoblasts, on the other hand, work in groups of connected cells during the formation of bone. Bone is not formed by individual cells. The osteon is a collection of organised osteoblasts and the bone generated by a unit of cells.

Mesenchymal stem cells produce osteoblasts, which are specialised, terminally differentiated materials.

They produce much smaller amounts of thick, crosslinked collagen and specialised proteins, such as osteocalcin and osteopontin, which make up the organic matrix of bone.

What is the Difference Between Osteoblast and Osteoclast?

What are the Similarities Between Osteoblast and Osteoclast Cells?

Following are the similarities between Osteoblast and Osteoclast Cells-

• Both osteoclast and osteoblast are bone cells.

• Both the cells are involved in bone remodelling and help repair bones.

• Both are metabolically very active and are nucleated.

• Both cells are located on the surface of the osteon seam.

• Both are connective tissue.

Pathological Conditions Related to Bones

To maintain proper bone mass and consistency, healthy bone remodelling entails firmly coupling resorption to formation. Several degenerative bone conditions may occur when this coupling mechanism is disrupted or osteoclast function is dysregulated.

1. Osteoporosis: This is the most common pathological disorder that affects the regulation of healthy bone content. An irregular rise in osteoclast activity is one of the symptoms. It causes a decline in bone material integrity, which makes fractures more likely. While ageing is the most common cause, other factors such as hormonal imbalance and oestrogen deficiency in postmenopausal women can also increase osteoclast activity.

2. Paget’s Disease: This is a deforming bone condition marked by a rise in the number and size of osteoclasts. It causes localised bone destruction and osteoblast activity to compensate. This disorder is caused by mutations in genes that control the development of osteoclasts.

3. Rheumatoid Arthritis: In the late stages of the disease, pathological osteoclasts become activated, resulting in painful and erosive lesions.