Osteoklasty

Osteoklasty is the process of bone resorption carried out by osteoclasts, large multinucleated cells derived from the monocyte–macrophage lineage. These cells reside on resorption bays, known as Howship’s lacunae, on mineralized bone surfaces and work in concert with osteoblasts during bone remodeling.

Formation and regulation of osteoclasts depend on two key signals. Macrophage colony-stimulating factor (M-CSF) promotes survival and proliferation of osteoclast precursors, while receptor activator of nuclear factor kappa-B ligand (RANKL) drives their differentiation. Osteoblasts and other stromal cells provide RANKL, and osteoprotegerin (OPG) acts as a decoy receptor to inhibit RANKL signaling, providing a siting check on osteoclast formation.

Structure and mechanism: osteoclasts attach to bone via integrins, forming a sealing zone and a ruffled border at the resorption surface. They secrete protons through V-ATPases and chloride channels to acidify the resorption lacuna, dissolving hydroxyapatite, and release proteolytic enzymes such as cathepsin K to degrade organic matrix. Digested material is endocytosed and transported to the cell surface for disposal.

Physiology and pathology: osteoclasts are essential for normal bone remodeling, mineral homeostasis, and recovery from microdamage. Imbalanced activity can cause disease: excessive resorption contributes to osteoporosis and osteolytic lesions in cancer, while insufficient activity leads to osteopetrosis. Treatments often target osteoclasts, including bisphosphonates that promote osteoclast apoptosis and denosumab, a monoclonal antibody that inhibits RANKL signaling.

See also: bone remodeling, RANKL, osteoprotegerin, cathepsin K, TRAP.