Q&A: How do osteoclasts resorb bone?
Author: Sanketh DS, MDS
Osteoclasts are large multinucleated giant cells having around 15-20 nuclei, whose function is to resorb bone. They play a very important role in bone remodelling and are characterised by the presence of an enzyme called tartrate resistant acid phosphatase (TRAP). Osteoclasts are haematopoietic in origin and are derived from the monocyte/macrophage lineage of cells.
FORMATION OF OSTEOCLAST
Bone marrow stromal cells and osteoblasts are responsible for secreting RANK ligand (RANKL) which combines with the RANK receptor on the osteoclast precursor. This induces a signalling cascade leading it to fuse with other precursor cells to form an osteoclast. The formation of osteoclast is regulated by several factors that include Vitamin D3, parathyroid hormone, prostaglandins and cytokines like IL-1, IL-6, TNF-α.
Bone resorption is the act of demineralization of the inorganic components and degradation of the organic components of the bone by osteoclasts. These osteoclasts can be seen occupying shallow depressions called “Howship’s lacunae” during active resorption of bone. After being recruited to the site of resorption, osteoclasts develop several invaginations on their plasma membrane facing the bone to be resorbed. This is called as the “ruffled border”. The plasma membrane of the osteoclast, then attaches to the bone, via proteins like osteopontin and bone sialoprotein (BSP). These attachments are called “sealing zones” or “clear zones”. Sealing zone helps form the resorption compartment or a closed and a sealed microenvironment between the osteoclast and the bone. The cytoplasm of the osteoclast consists of several nuclei surrounded by golgi complexes, rough endoplasmic reticulum and mitochondria.
Demineralizing inorganic material
The hydroxyapatite forming the inorganic material is removed by the action of hydrogen ions or protons. The hydrogen ions are derived from carbonic anhydrase in the cytoplasm of the cell and are pumped into the resorption compartment via proton pumps. This demineralizes the bone, exposing the organic matrix.
Degrading organic material
Organic matrix of the bone is removed by the action of several enzymes like acid phosphatase, cathepsin K and matrix metalloproteinase. These enzymes are formed in the rough endoplasmic reticulum, transported to the golgi complex where they are packaged into vesicles and are released via the ruffled border into the resorption compartment. On digestion of the organic matrix, the bone develops a shallow depression called “Howship’s lacunae”!
Removal of degradation products
Following resorption, the degraded products are endocytosed via the ruffled border, packed into vesicles and released extracellulary by exocytosis through the membrane opposite the ruffled border.
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