Osteoclastceller

Osteoclastceller, or osteoclasts, are multinucleated cells responsible for bone resorption. They originate from hematopoietic precursors of the monocyte/macrophage lineage and are located on the bone surface in regions of remodeling.

Osteoclastogenesis requires macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). RANKL binding to RANK on precursors activates NF-κB and NFATc1, promoting cell fusion and maturation. Osteoprotegerin (OPG) acts as a decoy receptor to inhibit RANKL signaling.

A mature osteoclast forms a sealing zone and a ruffled border on the resorption surface. It acidifies the microenvironment with proton pumps (V-ATPases) and chloride channels, and secretes proteolytic enzymes such as cathepsin K and metalloproteinases to degrade mineral and organic matrix. Resorption creates a pit known as a Howship lacuna.

Osteoclast activity is integrated with osteoblast activity during bone remodeling, and is modulated by hormonal and cytokine signals. Calcitonin inhibits resorption; parathyroid hormone, vitamin D, and estrogen deficiency can enhance it, while osteoprotegerin serves as a natural check by limiting RANKL availability.

Clinical relevance: Excessive osteoclast activity contributes to osteoporosis and inflammatory bone loss. Therapeutic approaches include denosumab, a monoclonal antibody against RANKL, and bisphosphonates that inhibit osteoclast function. Osteoclast-like cells are also observed in giant cell tumors and other lytic bone lesions.