Biomedical Engineering Reference
In-Depth Information
into the calcium pool and maintains the body's extracellular calcium levels
at a relatively constant level. This hormone can induce cytoskeletal changes
in osteoblasts, which are the only bone cells that have parathyroid hor-
mone receptors. Vitamin D stimulates intestinal and renal calcium-binding
proteins and facilitates active calcium transport. Calcitonin is secreted by
the parafollicular cells of the thyroid gland in response to an acutely ris-
ing plasma calcium level. Calcitonin serves to inhibit calcium-dependent
cellular metabolic activity.
Bone metabolism is also affected by a series of proteins, or growth factors,
released from platelets, macrophages, and fibroblasts. These proteins cause
healing bone to vascularize, solidify, incorporate, and function mechanically.
They can induce mesenchymal-derived cells such as monocytes and fibro-
blasts to migrate, proliferate, and differentiate into bone cells. The proteins
that enhance bone healing include the BMPs, insulin-like growth factors,
transforming growth factors, platelet derived growth factor, and fibroblast
growth factor, among others [12].
1.6.1 Parathyroid Hormone (PTH)
As one of the three important calcitropic hormones mentioned earlier,
PTH, or parathormone or parathyrin, is secreted by the chief cells of the
parathyroid glands as a polypeptide containing 84 amino acids. It is the
most important endocrine regulator of calcium and phosphorus concen-
tration in extracellular fluids. This hormone is secreted from cells of the
parathyroid glands and finds its major target cells in bones and kidneys.
Another hormone, the parathyroid hormone-related protein, binds to the
same receptor as a parathyroid hormone and has major effects on devel-
opment. Like most other protein hormones, the parathyroid hormone
is synthesized as a preprohormone. After intracellular processing, the
mature hormone is packaged within the Golgi (a Golgi apparatus repre-
sents a cytoplasmic organelle involved in the processing and sorting of
proteins and lipids) into regulated secretory vesicles and then secreted into
blood by exocytosis. A parathyroid hormone is secreted as a linear protein
of 84 amino acids.
PTH enhances the release of calcium from the large reservoir contained in
the bones [13]. Bone resorption is the normal destruction of bones by osteo-
clasts, which are indirectly stimulated by PTH. Stimulation is indirect, as
osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts,
the cells responsible for creating bones. Binding stimulates the osteoblasts
to increase their expression of RANKL (receptor activator of nuclear factor
kappa-B ligand) and inhibits their expression of osteoprotegerin (OPG). OPG
binds to RANKL and blocks it from interacting with RANK, a receptor for
RANKL. The binding of RANKL to RANK (facilitated by the decreased
amount of OPG) stimulates these osteoclast precursors to fuse, forming new
osteoclasts that ultimately enhance bone resorption.
