Bone Remodeling

Building off the last post, I'd like to segue into the mechanism of bone remodeling, or the process of removing old bone (resorption) and laying down new bone. This is a good transition because I already covered the 3 main cell types in bone: osteoblasts, osteocytes, and osteoclasts. Each has an important role in bone remodeling that I briefly touched on previously.

Why do bones need to remodel? 
What we think of when we hear 'remodeling' is a new kitchen, a living room, a basement, an office. A room wears down after continual use, gets old and outdated, and eventually needs a new look. The same sort of idea can be applied to bone matrix. Over time, bones sustain micro-damage and new bone matrix must be produced to maintain skeletal/structural integrity. In the case of injuries, such as fractures, remodeling can also replace bone that is damaged on a larger scale. Physiologically, this process also regulates blood calcium levels. There are 3 phases to bone remodeling: resorption, reversal, and formation.

Resorption: 
The cells responsible for resorption of bone are osteoclasts, which reside on the outer layer of bone. First, the osteoclasts bind to the osteons and induces an infolding of their cell membranes. They secrete enzymes that break down the matrix. This causes calcium, magnesium, phosphate, and collagen to be released into the extracellular fluid. Calcium is transferred into the blood to alter plasma calcium levels.

Reversal:
In the reversal phase, mononucleated cells appear on the surface of the bone or where the "resorption pit" is formed from osteoclast activity. These are most likely mesenchymal stem cells, which proliferate on site and then differentiate into osteoblasts.

Formation:
In the final phase, the osteoblasts fulfill their role by releasing osteoid, eventually hardens into bone matrix. The matrix mineralizes through the help of calcium and phosphorous.

Regulation
Signaling pathways of physiological processes can be intensely intricate and complicated, influenced by a variety of factors. The entire process of bone remodeling is still not fully fleshed out in detail, though much work is being done. Many hormones (parathyroid hormone, calcitrol, etc) and growth factors (TGF-βs, BMP, prostaglandins, etc) regulate bone remodeling. For example, how can osteoblasts form enough bone and tell osteoclasts to stop resorbing bone? After the reversal phase, when osteoblasts are differentiated, the cell presents a protein called receptor activator of NF-kB ligand (RANKL), which then binds to its receptor (RANK) found on osteoclasts. The binding of the RANKL upregulates osteoclast activity, meaning it increases it. Many degenerative bone diseases such as rheumatoid arthritis are caused by overproduction of RANKL (too much resorption of bone). However, osteoblasts can also produce a decoy RANKL protein that binds to the osteoclast receptor and inhibits the osteoclast's ability to bind to osteons and remove matrix, thus downregulating it's activity. Hormones can also affect RANKL (and other protein) expression. The osteoblast thus uses these methods to not only control bone matrix integrity, but also plasma calcium levels.


Sources:
Porter JR, Ruckh TT, Popat KC. Bone Tissue Engineering: A Review in Bone Biomimetics and Drug Delivery Strategies. Biotechnol Prog. 2009, Vol. 25, No. 6. 1539-1560. 
Wikipedia