Osteoclast (plural “osteoclasts”) is multinucleated cell present only in bones and osteoclast function is crucial in the body for bone absorption and regeneration. Bone is a dynamic connective tissue in vertebrates; in which, regulating the repair and remodeling of bones is very crucial process. Osteoclast function is to digest the bulk molecules of hydrated proteins and mineral into small elements by secreting enzymes, collagenase and acid phosphatase, and some potent acids; a process called as bone resorption.
- Osteoclast was discovered by Albert Kolliker in 1873 and proposed that osteoclasts function is mainly designed to digest the bone.
- The term “osteoclast” used in bone-cell biology and derived from Greek (osteo means “bone” and clast means “broken”).
- In vertebrates, bone development and bone resorption are closely coupled mechanisms that are responsible for bone remodeling.
- It are differentiated (or derived) from hemopoietic progenitor cells of the monocyte-macrophage
- It contains large number of cellular organelles such as mitochondria, lysosomes, and vacuole.
- Vacuole is very essential organelle in Osteoclast cell to digest the engulfed bone fragments.
- Osteoblasts are another type of bone cells involved in osteoclastogenesis through cell-to-cell contact with osteoclast progenitors.
- Osteogenesis imperfecta is a brittle bone disease caused due to genetical mutations especially the genes, COL1A1 and COL1A2 which are responsible for bone formation.
- Osteoporosis is another process in which rate of bone formation (osteogenesis) is lesser than bone resorption. The resulting conditions is lesser bone mass.
- Deficiency of estrogen enhances the activity of osteoclasts, that results into enhancement of osteoclast formation and bone resorption (2).
- In women, after menopause, the activity of osteoclasts is increased due to low level of estrogen at this point (3).
- Any alterations in testosterone levels in men may also increases the activity of osteoblast cell.
- These sex hormonal fluctuations in both men and women related to emerging bone problems including bone fractures or trauma.
- Femoston is a estrogen and progesterone-containing tablet; Femoston medication reduces the absorption and increase the bone strength.
- Odontoclasts is another type of cell that also show similar function in human deciduous teeth.
Where is osteoclast present and what is its main cellular character?
As mentioned above, osteoclast is a bone cell and present in pits of bone surface which are called resorption bays, or Howship’s lacunae. It contain homogeneous cytoplasm with foamy appearance. This foamy character of cytoplasm due to presence of more concentration of vesicles and vacuoles. The vacuoles such as lysosomes filled with enzyme, acid phosphatase. This acid nature of osteoblast allows us to identify these cells by using staining method to analyze the high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K. It contains thin rough endoplasmic reticulum and extensive Golgi complex.
Osteoclasts can synthesize numerous enzymes, e.g. acid phosphatase, that dissolves organic protein especially collagen as well as inorganic phosphorus and calcium of the bone. Mineralized bone is first broken down into small fragments then the osteoclasts engulf these fragments and send them to vacuoles. The further digestion takes place using enzymes of vacuoles. Calcium and phosphorus produced by the breakdown of the mineralized bone are released into the bloodstream. Unmineralized bone (osteoid) is protected from osteoclastic resorption.
Cathepsins are proteolytic enzymes involved in the collagen and other noncollagenous proteins. Especially Cathepsin K is major enzyme produced by osteoclast and involved in the bone resorption by degrading the bone structural proteins. Any mutation in the collagen gene related to pycnodysostosis, a hereditary osteopetrotic disease, which is result of defeciency in functional cathepsin K expression.
In acidic conditions, Cathepsin K will show its optimal enzymatic activity. Initially, cathepsin synthesized as proenzyme with a molecular weight of 37kDa, and latter it is activated by autocatalytic cleavage and generates ~27kDa weight active fragment. Once the active form is developed then it involved in proteolytic process.
Upon polarization of the osteoclasts at the site of bone resorption, cathepsin K is released into resorptive pit from the ruffled border. 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.
What are the metabolites that regulate osteoclast function?
Several hormones can regulate the osteoclast function, especially thyroid gland producing hormones such as parathyroid hormone (PTH) (from the parathyroid gland) and calcitonin (from the thyroid gland), and growth factor such as interleukin 6 (IL-6). IL-6 is one of the main factors in the osteoporosis disease, which is an imbalance condition between bone resorption and bone formation. While osteoclast function also regulated by the interaction of two molecules released from osteoblasts, namely osteoprotegerin and RANK ligand. The fact that these molecules also regulate the differentiation of osteoclasts.
Differentiation of osteoclasts occurs in two ways, which are defined based on osteoblast involvement.
1. Osteoblast dependent osteoclast differentiation
Recent studies on interactions between Receptor Activator of NF-Kappa B (RANK) and RANK Ligand (RANKL) discovered the well-known hypothesis that osteoblasts play an important role in osteoclast cell differentiation. Osteoblasts express a membrane-associated factor RANKL on their membranes. While, osteoclast precursor cells express a receptor, RANK on their membrane. RANKL and RANK interactions (cell-cell interaction) recognize and differentiate the osteoclast precursor cells into osteoclasts. Thus, osteoblast is also responsible for osteoclast differentiation.
2. Osteoblast-independent differentiation of Osteoclast
Also, recent studies have found that lipopolysaccharide and inflammatory cytokines including tumor necrosis factor receptor-alpha and interleukin-I directly induce the osteoclast differentiation and function, this mechanism is independent of the RANKL-RANK interaction. Interferon-gamma and transforming growth factor-beta super family members are also found to be important factors for osteoclastogenesis. These studies have provided new areas for analyzing the molecular mechanisms involved in the osteoblast and osteoclast differentiation (Katagiri and Takahashi).
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