Joseph L Roberts1,2, David N Paglia3, Hicham Drissi4,5,6. 1. Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA, USA. 2. Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA. 3. Department of Orthopaedics, New Jersey Medical School, Rutgers University, Newark, NJ, USA. 4. Department of Orthopaedics, School of Medicine, Emory University, Atlanta, GA, USA. hicham.drissi@emory.edu. 5. Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA. hicham.drissi@emory.edu. 6. Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA, 30033, USA. hicham.drissi@emory.edu.
Abstract
PURPOSE OF REVIEW: Growing evidence supports the critical role of transcriptional mechanisms in promoting the spatial and temporal progression of bone healing. In this review, we evaluate and discuss new transcriptional and post-transcriptional regulatory mechanisms of secondary bone repair, along with emerging evidence for epigenetic regulation of fracture healing. RECENT FINDINGS: Using the candidate gene approach has identified new roles for several transcription factors in mediating the reactive, reparative, and remodeling phases of fracture repair. Further characterization of the different epigenetic controls of fracture healing and fracture-driven transcriptome changes between young and aged fracture has identified key biological pathways that may yield therapeutic targets. Furthermore, exogenously delivered microRNA to post-transcriptionally control gene expression is quickly becoming an area with great therapeutic potential. Activation of specific transcriptional networks can promote the proper progression of secondary bone healing. Targeting these key factors using small molecules or through microRNA may yield effective therapies to enhance and possibly accelerate fracture healing.
PURPOSE OF REVIEW: Growing evidence supports the critical role of transcriptional mechanisms in promoting the spatial and temporal progression of bone healing. In this review, we evaluate and discuss new transcriptional and post-transcriptional regulatory mechanisms of secondary bone repair, along with emerging evidence for epigenetic regulation of fracture healing. RECENT FINDINGS: Using the candidate gene approach has identified new roles for several transcription factors in mediating the reactive, reparative, and remodeling phases of fracture repair. Further characterization of the different epigenetic controls of fracture healing and fracture-driven transcriptome changes between young and aged fracture has identified key biological pathways that may yield therapeutic targets. Furthermore, exogenously delivered microRNA to post-transcriptionally control gene expression is quickly becoming an area with great therapeutic potential. Activation of specific transcriptional networks can promote the proper progression of secondary bone healing. Targeting these key factors using small molecules or through microRNA may yield effective therapies to enhance and possibly accelerate fracture healing.
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