Anatomy & Organs

Osteoclasts – Structure, Function & Diseases

Osteoclasts

The osteoclasts are giant cells responsible for bone breakdown and demineralization. Their activity is regulated by various substances, such as parathyroid hormone. Too high or too low osteoclast activity shows serious effects on skeletal health.

What are osteoclasts?

Humans get a completely new skeleton every seven years . Human bones adapt to loads and are constantly being remodeled. After microfractures and fractures, they are renewed. The defective bone mass is removed and new bone mass builds up.

The so-called osteoblasts are responsible for the construction work . These are immature bone cells that later mature into osteocytes . It is not the osteoblasts that take over the breakdown work in the bone metabolism, but the osteoclasts. These bone cells arise from progenitor cells in the bone marrow and migrate to the skeletal system when needed. Her work involves two different mechanisms: the demineralization of bone substance and the actual breakdown of bone.

Osteoclasts slow down bone growth through their work and prevent excessive growth processes and proliferation. They communicate with the osteoblasts via the key substance RANKL. In addition to this communication, the hormonal cycle plays a role in their regulation. Parathyroid hormone activates degradation and calcitonin inactivates osteoclast activity.

Anatomy & Structure

Osteoclasts are multinucleated cells and are therefore classified as giant cells. They arise from the fusion of mononuclear progenitor cells in the bone marrow, also known as blood stem cells.They are part of the mononuclear phagocytic system. This means the entirety of all cells of the reticular connective tissue , parts of which are counted as part of the immune system and are responsible for breaking down and removing waste and foreign particles. Osteoclasts have a diameter of 30 to 100 µm and can contain more than 20 cell nuclei. They sit on the bone surface in the Howship lacunae and move amoeboid. Their apical pole one points to the bone. In the center is a zone containing vesicles with a cell membrane folded like a flower. This “ruffled border” is the site for bone resorption.

The periphery of the osteoclasts is intensely stained. The adhesion apparatus there allows the cells to adhere to the bone at a minimum distance of 0.3 nm. This “sealing zone” is enclosed by the cytoplasm , which is also called the “clear zone” and has only a few cell organelles but many contractile proteins .

Function & Tasks

The build-up and break-down processes of the bone substance are ideally coordinated and are controlled by a finely regulated control circuit. The osteoclasts are stimulated to form by various factors. Dexamethasone, 1,25-(OH)2VitD3, parathormone, PTHrP, prostaglandin-E2 and cytokines have a bone resorptive effect. Bisphosphonates, calcitonin and estrogens , on the other hand, have an inhibitory effect on the osteoclasts .

These factors regulate the activation of the so-called PU.1 transcription factor. It controls the conversion of bone marrow macrophages into multinucleated osteoclasts. The substances RANKL and osteoprotegerin are also involved in the activation. The hormonal control circuits use the bones as a kind of buffer to regulate the calcium balance. The bone resorptive parathyroid hormone releases calcium , for example . Calcitonin, on the other hand, stimulates the storage of calcium. The skeletal system adapts to loads and changes through the controlled, permanent build-up and breakdown of bone substance. Material fatigue is prevented in this way. A role in osteoclast regulation is now also being attributed to osteocytes.

Osteocytes are entrapped osteoblasts that have reached maturity. If a bone is affected by a fracture or microfracture, the osteocytes die off due to a lack of nutrient supply and the released substances call the osteoclasts into action. The work of the osteoclasts consists of two mechanisms. There is a minimal space between an osteoclast and the bone substance in which the pH value is reduced. Due to this degradation, the bones are demineralized. Mineral salts are extracted. The pH value required for this is kept constant by active proton transport. The osteoclasts detach the collagenous bone matrix by proteolytic enzymes. In doing so, they bring the collagen fragments released in this wayfor phagocytosis.

Diseases

When osteoclast activity falls or rises, this change can assume pathological proportions. Degradation and reconstruction are ideally coordinated in healthy bones.Reduced osteoclast activity can therefore cause just as much damage as increased activity. In the case of genetically determined osteopetrosis, for example, there is a greatly reduced osteoclast activity. In contrast, increased osteoclast activity is characteristic of non-genetic osteoporosis , hyperparathyroidism , osteodystrophia deformans and aseptic bone necrosis . The same applies to rheumatoid arthritis , periodontitis and osteogenesis imperfecta . With increased osteoclast activity, bone mass is broken down faster than it can be replenished.

Those affected therefore suffer from fragile and weak bones. In hyperparathyroidism , the regulatory apparatus of bone formation itself is affected. The epithelial bodies are abnormal and misregulate the calcium level in the body in the form of parathyroid hormone. This is caused by the increased secretion of parathyroid hormone, which is due to an adenoma or an enlargement of the parathyroid glands . Bone resorption is increased by the increased parathyroid hormone level. The result is severe bone pain and reduced calcium excretion in the kidneys . The amount of calcium in the blood continues to rise and causes kidney stones .

Typical & common bone diseases

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.