On the biochemical and biophysical front ...

It has long been established that bone possesses electromechanical properties and natural biopotentials that are essential in bone remodelling. These properties were first observed by Yasuda, Fukada, Bassett, Becker and others, who observed that repair and adaptive remodelling processes, occurred in response to mechanical loading, and furthermore, that such responses could be elicited by an electrical stimulus. In light of this, much work has been focused on the application of exogenous electrical currents, including pulsed electromagnetic fields (PEMF’s), to emulate the innate physiological and mechanical stresses evoked, and required in bone formation. Nowadays, researchers have expanded their visions, and are focusing on elucidating the mechanism of action of these fields, at the molecular level. Although several hypotheses have been proposed, the primary biochemical and biophysical effects, at the molecular, or ionic, level remain obscure.

Into the biological and biomolecular front ...

Endochondral bone formation occurs through a complex series of events, whereby mesenchymal precursors committed to prechondrogenic cells, undergo a series of both morphological and biochemical modifications, in response to extrinsic factors (matrix molecules, growth factors and cytokines), modulated in an autocrine/paracrine manner, to progress from undifferentiated cells to hypertrophic chondrocytes or osteoblasts. Differentiation therefore, depends on microenvironmental factors. Bone marrow stromal cells (BMSC) have the potential, not only to differentiate into osteoblasts, but into chondrocytes too. In fact, they have been extensively demonstrated to have the potential to differentiate into specialized connective tissue cells and to give rise to skeletal tissues. Several factors, including growth factors, affect BMSC proliferation rate and osteogenic potential, however, it has never been established whether these same factors affect BMSC chondrogenic potential too. In a study by Mastrogiacomo2 and colleagues, 2001, FGF2 (fibroblast factor 2), PDGFbb (platelet derived growth factor BB), EGF (epidermal growth factor) and IGF (insulin-like growth factor), were assessed for their affect on BMSC as to affecting both their osteogenic and chondrogenic potential. It was found that FGF2 was the most effective in maintaining BMSC in an immature state as chondro-osteoprogenitor cells, and that reconstitution of cartilage parallels that of bone.

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