Osteoclasts are giant cells responsible for bone resorption 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?
Every seven years, humans receive an entirely new skeleton. Human bones adapt to stresses and are permanently remodeled. They are renewed after microfractures and fractures. The defective bone mass is removed and new bone mass is built up. The so-called osteoblasts are responsible for the build-up work. These are immature bone cells that later mature into osteocytes. The degradation work in bone metabolism is not carried out by osteoblasts, but by osteoclasts. These bone cells arise from precursor cells from the bone marrow and migrate into the skeletal system as needed. Their 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 osteoblasts through the key substance RANKL. For their regulation, besides this communication, the hormonal cycle plays a role. Parathyroid hormone activates degradation and calcitonin inactivates osteoclast activity.
Anatomy and structure
Osteoclasts are multinucleated cells and thus belong to the so-called giant cells. They are formed by the fusion of mononuclear progenitor cells in the bone marrow, also known as hematopoietic stem cells. They are a part of the mononuclear-phagocytic system. This refers to the totality of all cells of the reticular connective tissue, parts of which are considered part of the immune system and are responsible for the breakdown and removal of waste and foreign particles. Osteoclasts have a diameter of 30 to 100 µm and can contain more than 20 cell nuclei. They are located on the bone surface in the howship lacunae and move amoeboid. Their apical pole of one faces the bone. Centrally, there is a vesicle-containing zone with a flower-shaped folded cell membrane. This “ruffled border” is the site of bone resorption. The periphery of the osteoclasts is intensely stained. The adhesion apparatus there allows the cells to adhere to the bone with a minimal distance of 0.3 nm. This “sealing zone” is enclosed by cytoplasm, also called the “clear zone,” which has few cell organelles but many contractile proteins.
Function and tasks
The processes of formation and degradation of bone substance are ideally coordinated and controlled by a finely regulated regulatory circuit. Osteoclasts are stimulated to form by various factors. Dexamethasone, 1,25-(OH)2VitD3, the parathyroid hormone, PTHrP, prostaglandin-E2 and cytokines have a particularly resorptive effect on bone. In contrast, bisphosphonates, calcitonin and estrogens have an inhibitory effect on 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 activation. The hormonal regulatory circuits use bone as a kind of buffer to regulate calcium balance. The bone-resorptive parathyroid hormone, for example, releases calcium. Calcitonin, on the other hand, stimulates the storage of calcium. The permanent build-up and breakdown of bone substance controlled in this way enables the skeletal system to adapt to stresses and changes. In this way, material fatigue is prevented. Meanwhile, osteocytes are also thought to play a role in osteoclast regulation. Osteocytes are trapped osteoblasts that have reached maturity. When a bone is affected by a fracture or microfracture, the osteocytes die due to lack of nutrients, and the substances they release call the osteoclasts into action. The work of osteoclasts is composed of two mechanisms. Between an osteoclast and the bone substance there is a minimal space in which the ph-value is lowered. 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 collagenous bone matrix is detached by osteoclasts through proteolytic enzymes.In the process, they bring the collagen fragments thus released to phagocytosis.
Diseases
When osteoclast activity falls or rises, this change can take on pathologic proportions. In healthy bone, degradation and reconstruction are ideally matched. Therefore, decreased osteoclast activity can cause as much damage as increased activity. In genetically determined osteopetrosis, for example, there is greatly reduced osteoclast activity. Increased osteoclast activity, on the other hand, is characteristic of non-genetic osteoporosis, hyperparathyroidism, osteodystrophia deformans, and aseptic bone necrosis. The same is true for rheumatoid arthritis, periodontitis, and osteogenesis imperfecta. With increased osteoclast activity, bone mass is degraded faster than it can be replenished. Affected individuals therefore suffer from fracture-prone and weak bones. In hyperparathyroidism, the regulatory apparatus of bone formation itself is affected. The epithelial cells are abnormal and thus misregulate the calcium level in the body in the form of the parathyroid hormone. The cause is the increased secretion of parathormone, which is due to an adenoma or an enlargement of the parathyroid glands. The increased parathyroid hormone level increases bone resorption. The result is severe bone pain and decreased calcium excretion in the kidney. Thus, the amount of calcium in the blood continues to increase, causing kidney stones.
Typical and common bone diseases
- Osteoporosis
- Bone pain
- Bone fracture
- Paget’s disease
