Osteoclasts - Everything You Need To Know - Dr. Nabil Ebraheim

Dr. Ebraheim's educational video describing Osteoclasts - bone absorption.
The origin of osteoclasts my come from fusion of the macrophages/monocytes. As many as 50 of the cells fuse together to form a giant osteoclast cell. Osteoclast cells absorb bone. The lifespan of osteoclasts is a few days. One osteoclast can create a lot of damage. It will take three months to replace the bone that has been removed within only a few days by the osteoclasts. It may take 100-150 osteoblasts to replace the bone that has been removed by one osteoclast. The osteoclast cell has a lot of mitochondria (it is actually a machine). The osteoclasts is found against the bone surface in a hollow depression called the Howship’s Lacunae (where bone resorption occurs). The Howship’s Lacunae is the site of bone resorption where the ruffled border meets the bone surface. When the osteoclast absorbs the bone, it develops a ruffled border and a sealing zone.
Osteoclasts secrete two enzymes:
Cathespin K (CTSK) is an enzyme that is release by the osteoclast at the ruffled border and it absorbs the osteoid. Mutation of the gene that codes the enzyme Cathespin K (CTSK) will lead to a problem of the bone called pycnodysostosis. Another enzyme is secreted by the osteoclast is Tartrate-Resistant Acid Phosphatase (TRAP), which dissolves the hydroxyapatite crystals.
The osteoclasts attach themselves to the bone by two proteins (anchoring proteins). Osteoclasts bind themselves to the bone via integrin (protein). Vitronectin is on the bone and helps to attach the osteoclasts to the bone. Vitronectin and Integrin lock together to create a sealing zone. The osteoclast creates an acidic environment by producing hydrogen atoms through the carbonic anhydrases. This occurs by sealing the space below the osteoclast and lowering the pH level, increasing the solubility of the hydroxyapatite crystals. The matrix is also degraded by Cathespin B. Cathespin B (lysosomal enzyme) is another enzyme that works on the organic material. Deficiency of carbonic anhydrase leads to osteopetrosis.
What is the clear zone? The osteoclast binds to the bone through cell attachment utilizing anchoring proteins. The clear zone is the cytoplasmic area presenting the adhering plasma membrane, or the sealing membrane, which surrounds the ruffled border and seals the absorbing compartment.
The osteoclast has two centers on its surface:
Calcitonin receptor inhibits the osteoclast. The RANK receptor binds to the RANK ligand on the surface of the osteoclast and stimulates the osteoclast. RANK ligand comes from the osteoblasts and the tumor cells. RANK ligand which binds to the receptor of the osteoclast, will stimulate the differentiation and activation of the osteoclast and increase bone resorption. The RANK ligand function is inhibited by osteoprotegerin (OPG). This action of blocking the binding of RANK ligand to RANK reduces osteoclast activity.
What is really against the osteoclast (osteoclast inhibition)?
•Osteoprotegerin (OPG)
oSecreted by the osteoblast
oProtects us from excessive bone loss by blocking RANK L
oThe balance between OPG and RANK L is important!
•Calcitronin
•Interleukin 10 (IL-10)
•Denosumab
oMonoclonal antibody to RANK ligand
oIt is like an OPG, which is the decoy receptor that prevents RANK L signaling.
•Bisphosphonate
oPrevents the osteoclasts from forming the ruffled border and producing acid phosphatases
oIt may also cause death of the osteoclast
Osteoclast Stimulation and Activation
•RANK L
oStimulates the osteoclast
oThe osteoclast activity is controlled by the osteoblasts, which is controlled by the parathyroid hormone.
•Interleukin 1 (IL-1)
oStimulates the osteoclast
oIt is found at the membrane of loose total joints
•Macrophage Colony-Stimulating Factor (M-CSF)
oCofactor required for the action of the osteoclast.
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