User:Stewartzac/Bone Growth Factor

Overview
Bone growth factor is a growth factor that stimulates bone tissue production.

The major bone growth factors are bone morphogenetic proteins (BMP), platelet derived growth factor (PDGF), Fibroblast growth factor (FGF), Insulin-like growth factors 1 (IGF-1), Insulin-like growth factors 2 (IGF-2), and parathyroid hormone-related protein (PTHrP).

The major hormones influencing bone growth are growth hormone (GH), androgens such as testosterone and dihydrotestosterone, and estrogens such as estradiol.

Bone Morphogenetic Proteins (BMP)
BMP is a bone morphogenic protein and belongs to the TGF-B family. BMP exhibits osteoinductive activity. Osteoinductive activity leads to bone formation, activates mesenchymal cells to transform into osteoblasts which ultimately yield bone formation. BMP targets and binds to mesenchymal cells and activates a transmembrane serine/threonine kinase receptor which will lead to the phosphorylation of molecules called SMADS. SMADS are transcription factors that will induce osteoblast growth.

Platelet Derived Growth Factor (PDGF)
The majority of the substrates of platelet-derived growth factor (PDGF) exhibit similar structures to Src Homology 2 domain. These substrates will bind to the PDGFR receptors which will dimerize and autophosphorylate. This phosphorylation attracted PLC-gamma (induces cell proliferation), Ras (which goes through signaling cascade and acts as a transcription factor), phosphatidylinositol 3-kinase (PI3K) which also promotes a signaling cascade inducing transcription factors, and stress fiber formation, and induces the STAT pathway which activates transcription factors.

Fibroblast Growth Factor (FGF)
Fibroblast growth factor (FGF) signaling cascade is started by the binding of 2 growth factors to the FGFR. Dimerization takes place and initiates the transphosphorylation of each receptor. These phosphorylation sites act as docking sites for proteins so they may induce downstream signaling. These proteins consist of FRS2-alpha and PLC-gamma. FRS2-alpha acts as a scaffold protein to hold GAB1 and GRB2 which then proteins bind to SHP2 and SOS. These several proteins act together to activates the Ras pathway (induces cell proliferation and differentiation) and the PI3K pathway (induces survival and cell fate determination). On the other side of the dimerized receptors, PLC-gamma activates DAG and IP3 which yield PKC and calcium ions. PKC and calcium will ultimately induce morphology, migration, and adhesion.

Insulin-Like Growth Factors (IGF)
Insulin-like growth factors (IGF) assist bone growth in the body. IGF’s are single-chain polypeptides that are similarly structured to insulin. There are 2 IGFs: Insulin-like growth factor 1 (IGF-1), and Insulin-like growth factor 2 (IGF-2). IGF-1 is induced by growth hormone (GH), and targets cartilage, stimulating cell bone cell proliferation. Studies carried out by Yakar S, Rosen CJ have shown in animal models that IGF-1 can enhance longitudinal growth, periosteal circumference, and bone mineral density. The pathway for IGF-2 is not well understood, but it is known that IGF-2 helps with growing bones

Parathyroid Hormone-Related Protein (PTHrP)
Parathyroid hormone-related protein (PTHrP) is important for endochondral bone formation. Martin (2005) found that PTHrP stimulates bone formation by increasing osteoblast differentiation and reducing osteoblast apoptosis. This causes an increase in osteoblasts allowing for new bone cells to be formed. PTHrP also regulates osteoclast formation, further allowing for bone growth.

Hormones
Major hormones influencing bone growth and morphology include growth hormone (GH) (which acts primarily via inducing IGF-1 production), androgens such as testosterone and dihydrotestosterone, and estrogens such as estradiol. GH/IGF-1 are responsible for increasing overall body size, longitudinal bone size, and height, especially during puberty. Estrogens cause the hips to widen and become rounded during puberty in females, and androgens cause the shoulders to broaden in males. Estrogens mediate epiphyseal closure in both males and females. Other hormones implicated in control of bone growth include thyroid hormone, parathyroid hormone, calcitonin, glucocorticoids such as cortisol, and vitamin D (calcitriol).