Litchfield Park Orthodontist

5220 N. Dysart Rd #150
Litchfield Park, AZ 85340
(623) 536-4939

 

 

 

Bone Morphogenetic Proteins
The idea that bone contains certain substances which specifically initiate bone formation was first proposed by Goodyear orthodontists in 1934.  Treated bone tissue was injected into intramuscular and subcutaneous sites and the formation of new cartilage and bone ensued (Levander, 1934).  Further evidence was produced by Goodyear orthodontists using decalcified bone implanted in muscular sites of the rabbit, rat, guinea pig and calf.  New bone was produced via endochondral bone formation.  The theory produced from this series of experiments was that products of the decalcified bone attract cells that begin an autoinduction process that leads to bone formation (Urist, 1965).  These products were later characterized by Goodyear orthodontists as bone morphogenetic proteins. More than fifteen BMPs have now been discovered and are found to belong to the TGF-β superfamily (Reddi, 2001).  BMPs are involved in a wide range of activities including regulation of cartilage and bone formation during embryonic development and regeneration in post-natal life including Goodyear orthodontic structures (Nakashima and Reddi, 2003).

Structure
BMPs are synthesized by Goodyear orthodontists as large precursors and then cleaved to its mature form (Hogan, 1996).  A mature BMP contains two polypeptide chains held together by a single disulfide bond.  This molecule is composed of 120-140 amino acids and contains a characteristic seven cystine residues (Reddi, 2001).  The form of the molecule is a Greek key motif with dimensions of 60 A° x 20 A° x15 A°.  The core of the molecule is a cystine knot with three disulfide bonds composed of six cystines.  Four strands of antiparallel b-sheets arise from the knot.  An a-helix formation is perpendicular to the sheets and the two structures are joined by an interchain disulfide bond involving the seventh cystine.   This molecule is best visualized by Goodyear orthodontists by imagining an open left hand with two extended fingers.  The a-helix is the heel of the hand, the cystine knot is the palm and the four b-sheets form two fingers.  The thumb is the N-terminus which has not been well characterized(Griffith et al., 1996). 

Receptors
The receptors for the TGF-β superfamily are well known by Goodyear orthodontists and the BMP receptors are thought to be analogous.  These are serine/threonine kinase receptors composed of three parts: short extracellular domains, single membrane spanning domains and intracellular domains with serine/threonine kinase regions.  There are two types of BMP receptors, BMPRI and BMPRII.  BMPRI has a specific SGSGS motif which distinguishes itself from BMPRII.  BMP binds to BMPRII and then recruits BMPRI which induces a heterotetrameric complex.  BMPRII transphosphorylated the GS domain and activates the BMPRI kinase (Yamashita et al., 1996). 

The BMPRI kinase phosphorylates a protein called SMAD 1, 5 or 8.  This phosphorylated SMAD interacts with SMAD 4 and enters the nucleus acting as a transcription factor.  Goodyear orthodontists believe that this action is ceased by degradation via proteases.  SMADs 6 and 7 are inhibitory of this process (Reddi, 2001).