Osteoclast
An osteoclast is one of the bone cells. Its function is the resorption of bone tissue over a process called remodelling. This process, in which osteoclasts reabsorb bone and osteoblasts synthesise new organic components in the bone matrix, is essential to the conservation of calcium Homeostasis and for the preservation of the integrity of the skeleton.
Morphology
Osteoclasts are mobile cells, rounded and giant (50 to 100 µm). They are extensively branched and multinucleated (6 to 50 nuclei). They have a Golgi apparatus very developed, numerous perinuclear mitochondria as well as a large amount of lysosomes.
The active osteoclast presents polarity. It has, in the side facing the bone, a “brush border” characterised by the presence of numerous villous extensions.
Origin and regulation
Osteoclasts have a haematopoietic origin from the myeloid lineage. Their precursors are derived from pro-monocytes that differentiate into monocytes/macrophages, dendritic cells or osteoclasts depending on the factors within its microenvironment. This process, called osteoclastogenesis, is regulated by different cells, in particular by osteoblasts and bone marrow stromal cells.
Osteoblasts and stromal cells stimulate the osteoclasts differentiation and proliferation through contact with the precursor cells and the release of M-CSF (macrophage colony stimulating factor) and RANKL, the RANK (Receptor Activator of Nuclear Factor kB) ligand.
M-CSF factor is essential in the first steps of osteoclastogenesis, increasing the survival rate of osteoclast precursors. RANKL is part of the superfamily of tumor necrosis factor ligands, TNF (tumor necrosis factor), its connection to RANK on the surface of the precursor cells induces, together with M-CSF, the expression of genes that typify the osteoclastic lineage: TRAP (tartrate-resistant acid phosphatase), CATK (cathepsin K), CTR (calcitonin receptor), CA2 (carbonic anhydrase 2), β3 class integrins, among others.
Other factors are also involved in osteoclasts differentiation such as cytokines, systemic hormones or growth factors.
The osteoclast precursors migrate, via chemotactic stimuli, through the bloodstream to the bone. They adhere to the surface and merge forming mature multinucleated osteoclasts.
The differentiation and proliferation of osteoclasts are inhibited by osteoprotegerin (OPG), synthesised by osteoblast-lineage cells, through its connection to RANKL, preventing its action. The amount of OPG increases with the degree of osteoclast differentiation thus maintaining a balance between bone resorption and new bone synthesis.
Function
During the process of reabsorption, the activated osteoclasts move along the surface of the bone forming multiple cavities called Howship lacuna. The activity of resorption is thereby alternated with periods of migration.
Bone resorption is carried out in 2 steps:
- The degradation of the inorganic portion of the matrix: Osteoclasts secrete, through carbonic anhydrase 2 activity, a large amount of protons. The acidification of the resorption compartment causes the dissolution of calcium phosphate crystals ;
- The degradation of the organic portion of the matrix: Hydrolytic enzymes, such as cathepsins and collagenases, are released to digest the demineralised matrix proteins.
On average, osteoclasts live 15 days after which they die by apoptosis.
References:
- Barond, R. (2001). L’ostéoclaste et les mécanismes moléculaires de la résorption osseuse. médecine/sciences. 17 (12), p1260-1269.
- Boissy, P., Malaval, L. and Jurdic, P. (2000). Ostéoblastes et ostéoclastes: une coopération exemplaire entre cellules mésenchymateuses et cellules hématopoïétiques. Hématologie. 6 (1), p6-16.
- Boyle, W.J., Simonet, W.S and Lacey, D.L. (2003). Osteoclast differentiation and activation. Nature. 423, p337-342.
- Couret, I. (2004). Biologie du remodelage osseux. Médecine nucléaire. 28 (2), p57-65.
- Junqueiro, L. and Carneiro, J. (2004). Histologia Básica. Rio de Janeiro: Guanabara Koogan. p136-139.
