A bone has two important cells; osteoclasts and osteoblasts.
Osteoclasts are irregular shaped giant cells that break down or reabsorbs the bone. Osteoblasts are cells that are responsible for new bone formation. Osteoclasts arise from either macrophages or monocytes. Monocytes fuse together to form multinucleated osteoclast cells.
Osteoclast cells have a “ruffled border” which touches the bone and increases the surface area for absorption of the bone.
Osteoclasts bind themselves to the bone via integrin (protein). Vitronectin helps to attach the osteoclasts to the bone.
The bone is absorbed at the Howship’s Lacunae. As the ruffled border of the osteoclast contacts the bone, it secretes acids that lower the pH level, and the osteoclasts then absorbs the mineralized bone matrix.
Cathepsin K (CTSK) is an enzyme that removes the bone at the ruffled border. Osteoclasts secrete tartrate resistant acid phosphates. Osteoclasts are unable to absorb unmineralized osteoid. Osteopetrosis, or “stone bone” occurs due to a deficiency in carbonic anhydrase.
There are proteins that interact with the osteoclasts and osteoblasts to control bone reabsorption. The osteoclast has RANK receptors on its surface. RANK Ligand is a protein given off by osteoblasts and tumor cells which is important to the formation and regulation of osteoclast activity. RANK Ligand proteins interact with the RANK receptors on the surface of the osteoclast.
Osteoprotegerin (OPG) is another protein that is secreted by the osteoblasts that blocks the binding of the RANK Ligand to RANK. The OPG protein is a decoy that stops the osteoclast from differentiation, fusion and activation, which causes a decrease in bone reabsorption and destruction. This action of blocking the binding of RANK Ligand to RANK reduces the osteoclast activity. Excessive amounts of RANK Ligand leads to more osteoclasts and greater bone loss.
Osteoclast Inhibition
There is a receptor for calcitonin on the osteoclast surface that inhibits bone resorption. Bisphosphonate (pamidronate) prevents the formation of the ruffled border and may cause apoptosis (death of the cell). Interleukin-10 (IL-10) suppresses the osteoclast activity. Osteoprotegerin (OPG) blocks the binding of RANK Ligand to RANK. Transforming Growth Factor Beta increases the OPG. Estrogen decreases RANK Ligand expression by the osteoblasts and decreases activity of adenylyl cyclase.
Osteoclast Activation
The Parathyroid hormone-related protein (PTHrP) is secreted by many cancer cells, including breast cancer. It utilized adenylyl cyclase and bines to a receptor of the osteoblast to produce RANK Ligand. RANK Ligand will go to an osteoclast and get attached to RANK for activation of the osteoclast. Interleukin 1 (IL-1) will contribute to total joint loosening. 1,25 Dihydroxy Vitamin D increases the production of RANK Ligand. IL-6 (myeloma) in tumors, especially myeloma. Prostaglandin E2 activates adenylyl cyclase.
