ROLE OF PDGF IN BONE REPAIR
Bone repair is a multi-step process that progresses over a period of weeks to months. Following an injury to bone, a hematoma (blood clot) is formed. As part of the clotting process, platelets are activated and degranulate, releasing a number of critical growth factors such as PDGF. Coinciding with a hematoma, an inflammatory response is initiated. At the inflammatory stage, cells such as macrophages, neutrophils and fibroblasts are activated to remove damaged tissue and stabilize the blood clot.
Throughout the granulation stage, stem cells directly involved with bone formation (osteoprogenitor cells) are recruited to the site of injury through a signaling mechanism known as chemotaxis and are induced to divide and increase in number (mitogenesis). Further, new capillaries and blood vessels begin to form (angiogenesis).
Differentiation factors (i.e. BMPs, GDFs, TGF-β) activate the transformation of osteoprogenitor cells into osteoblasts, which in turn initiate the production of extracellular matrix, or soft callus. Over time, the soft callus is calcified (mineralized) to form a hard callus of woven bone. In the final stage, bone remodels into a natural structure, regaining its pre-injury strength and function.
The principal actions of PDGF – chemotaxis, mitogenesis, and promotion of angiogenesis, start the bone healing cascade. Collectively these actions ensure an adequate number of appropriate cell types are available to drive all phases of the bone healing process.
A schematic of the bone repair process is shown below:
The influence of PDGF on bone formation has been the subject of a number of pre-clinical studies. In the following experiment, a femur (leg) fracture was simulated in a diabetic rat (a model associated with poor fracture healing outcomes).
The above images demonstrate that rhPDGF-BB at both doses resulted in more complete healing of the fracture gap where as the control samples demonstrated an absence of healing.
Additional citations for studies with rhPDGF-BB may be found in the Scientific Literature portion of this website.
1Al-Zube, L. et al. (2009), Journal of Orthopaedic Research.