OSTEOCLASTS: FORMATION, CHARACTERISTICS, FUNCTIONS, DISEASES - BIOLOGY - 2025

The osteoclasts are one of three types of cells found in bone tissue and are responsible for a phenomenon known as bone resorption, essential to maintain the structure of this.

Unlike osteoblasts and osteocytes, the other two cell groups present in bone tissue, osteoclasts, once they have fulfilled their function of resorption, go through complex processes of programmed cell death (apoptosis).

Microscopy of an active osteoclast (Source: Robert M. Hunt at English Wikipedia via Wikimedia Commons)

Its activity is regulated mainly by the endocrine pathway, specifically controlled by two hormones: parathyroid hormone and calcitonin, produced by the parathyroid and the thyroid gland, specifically.

The name of these cells was coined by Kölliker in 1873, and the role of bone resorption was initially attributed to osteocytes and macrophages, however, today it is known that these cells are rather "accessory" in this process.

They are elementary cells in skeletal physiology and defects in their function or abnormalities in the processes of which they are in charge imply the development of severe pathologies in humans.

Training

Osteoblasts are derived from mononucleated cells originating from the spinal cord and other hematopoietic organs, which are capable of migrating to bone tissues through vascular pathways.

They are formed from a progenitor cell called granulocyte-macrophage, which gives rise to osteoclasts and monocytes, whose proliferation and differentiation depend on different regulatory molecules, among which many cytokines can be named.

After the progenitor cells are disseminated through the vascular system, they establish in different areas of the bone tissue (the periosteum, endosteum and perichondrium).

Mononuclear phagocytes are very similar to pre-osteoclastic cells, but it is the bone microenvironment that determines their differentiation through different stimuli.

Progenitor cell differentiation

The pluripotent hematopoietic cells of the bone marrow receive signals that direct their development towards the myeloid lineage, which requires the expression of certain molecules that allow these cells to respond to osteoclastogenic factors.

As the myeloid cell "colony" differentiates, numerous markers for the macrophage lineage can be identified, characterized especially by the presence of a factor known as the "macrophage colony stimulating factor".

The importance of this factor in the differentiation of osteoclast-progenitor cells has been demonstrated through various experimental observations in animals with mutations in the related genes, who present severe abnormalities in bone development.

Progression of "macrophages" towards osteoclasts

Macrophages that are destined to differentiate in the osteoclast lineage progress toward the development of phenotypic characteristics inherent in these bone cells, such as the expression of the receptor for calcitonin and the ability to reabsorb bone.

At present, many research groups have determined that the main osteoclastogenic factor is one known as activator receptor ligand NFkB (RANKL, of the English " R eceptor A ctivator of N F k B L igand"), a membrane protein expressed after the stimulation of hormones or bone absorption cytokines.

This factor acts by many different indirect downstream pathways, modulating the expression of the genes necessary for the differentiation of osteoclasts and its expression also depends on the control of other molecules.

Differentiation then occurs progressively and another key step in the process is the fusion of multiple cells committed to the osteoclast lineage to form the "polykaryon" or multinucleated progenitor cell.

characteristics

Osteoclasts are multinucleated "giant" cells (with many nuclei) between 10 and 100 µm in diameter, with an acidophilic cytoplasm and that have a complex and specialized internal membranous system that functions in the resorption process.

They are mobile cells that move on the surface of the bones between the sites of resorption. When viewed in their active state, they have many vacuoles and mitochondria within them, which account for a high metabolic flux.

These cells occupy specific locations known as "Howship Lagoons", which are hollow depressions characteristic of the regions where bone resorption occurs.

Cross section of an active osteoclast (Source: Cellpath via Wikimedia Commons)

They are polarized cells, so that the organelles inside are found in certain areas: the basal area, the "curly edge" or "brush edge" area, the light area and the vesicular area.

The clear areas and the brush edges have specialized resorption structures that characterize them, which are observed as a network of membranous folds under which the resorption processes occur, since they are in direct contact with the bone.

The basal zone (furthest from the lagoons) is the one that contains the greatest amount of organelles: the nuclei and all related systems, while the vesicular zone consists of many transporter vesicles that collaborate with resorption and are located between the basal zone. and the brush edge.

Features

In conjunction with the other cells of bone tissue, as well as in concert with some local regulatory factors and certain hormones, osteoclasts play an important role in the structural maintenance and remodeling of bones, during and after osteogenesis.

In this sense, osteoclasts participate in the coupled resorption and formation process, which consists of osteoclast-mediated resorption and osteoblast-directed formation.

Broadly speaking, osteoclast-mediated bone resorption mechanisms involve secretion of hydrolases from their lysosomes and of ions that disintegrate bones.

Like other connective tissue cells, osteoclasts participate in the maintenance of calcium homeostasis in serum.

Diseases

Different diseases are related to the function of osteoclasts, among them are:

- Osteoporosis: it is a condition characterized by an imbalance between bone resorption and formation, where there is an exacerbated resorption, which produces fragility and continuous skeletal fractures. It commonly occurs in the elderly and elderly.

- Osteopetrosis: it is a genetic condition characterized by an increase in bone mass due to defects in the development of the curly edges of the osteoclasts caused by specific mutations, which results in a decrease in their resorption capacity.

- Paget's disease: it is detected in elderly patients as uncontrolled bone resorption and formation that apparently has a viral origin.

References

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