Osteoclast

The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption.

On such surfaces, the osteoclasts are seen to be located in shallow depressions called resorption bays (Howship's lacunae).

The periphery of the ruffled border is surrounded by a ring-like zone of cytoplasm which is devoid of cell organelles but is rich in actin filaments.

The actin filaments enable the cell membrane surrounding the sealing zone to be anchored firmly to the bony wall of Howship's lacunae.

The osteoclasts pump hydrogen ions into subosteoclastic compartment and thus create an acidic microenvironment, which increases solubility of bone mineral, resulting in the release and re-entry of bone minerals into the cytoplasm of osteoclasts to be delivered to nearby capillaries.

When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 μm in diameter occur.

These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate.

RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts.

Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK.

Osteoclasts lie in small cavities called Howship's lacunae, formed from the digestion of the underlying bone.

The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled border into the resorptive cavity, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances.

Cathepsin K is a collagenolytic papain-like cysteine protease that is mainly expressed in osteoclasts, and is secreted into the resorptive pit.

Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory domain.

Within these intercellular vesicles, cathepsin K, along with reactive oxygen species generated by TRAP, further degrades the bone extracellular matrix.

[15][16] With the successful culture of osteoclasts, it became apparent that they are organized to support the massive transport of protons for acidification of the resorption compartment and solubilization of the bone mineral.

This includes ruffled border Cl− permeability to control membrane potential and basolateral Cl−/HCO3− exchange to maintain cytosolic pH in physiologically acceptable ranges.

Developing the highly invaginated ruffled membrane apposing the resorption compartment allows massive secretory activity.

In addition, it permits the vesicular transcytosis of the mineral and degraded collagen from the ruffled border to the free membrane of the cell, and its release into the extracellular compartment.

[21][22] This activity completes the bone resorption, and both the mineral components and collagen fragments are released to the general circulation.

[23] Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANK ligand.

Osteoclasts play a major role in orthodontic tooth movement and pathologic migration of periodontally compromised teeth.

Tartrate resistant acid phosphatase positive osteoclast in cell culture
Illustrated cross-section of an activated osteoclast