BONE REGENERATION USING PATHOGENETIC CUES

Bone regeneration is pivotal for the healing of fractures. In case this process is disturbed a non-union can occur. This can be induced by environmental factors such as smoking, overloading etc. Co-morbidities such as diabetes, osteoporosis etc. may be more intrinsic factors besides other disturbances in the process. Those pathways negatively influence the bone regeneration process. Having knowledge on the pathogenetic pathways can be of advantage to use them as possible therapy options. Several intrinsic signal transduction pathways (WNT, BMP etc.) can be affected. Furthermore, on the transcriptional level, important mRNA expression can be inhibited by deregulated miRNA levels. For instance, several miRNAs have been shown to be upregulated in osteoporotic fractures. They are detrimental for osteogenesis as they block bone formation and accelerate bone resorption. This occurs on different levels from matrix production, signal transduction, cell differentiation etc. Modulating those miRNAs may revert the physiological homeostasis. The strength of modulating miRNAs is the fact that one miRNA has several mRNA targets. Thus, by modulation a single miRNA, several pathways will be influenced. Of note, physiological fracture healing has a typical miRNA signature. During the subsequent phases of fracture healing, different miRNAs are expressed. The expression is associated to the different processes that take place such as hemostasis, inflammation, proliferation and differentiation, and remodelling. When a miRNA is wrongly regulated, fracture healing is compromised. Reconstituting the correct miRNA signature could help to regenerate the bone. Thus, fractures are a diverse entity. Nevertheless, there seem to be common pathogenetic disturbances. The involved pathogenetic cues are important to understand where it goes wrong. Those can be counteracted at several levels from molecular to cell in order to re-establish a proper bone regeneration. Compositions of those may be the best option for future therapies. They can also be used in a more personalized fashion in case more specific measurements such as miRNA signature and stem cell activity are applied.