Transcriptomic Profiling of Bone Healing in Patients with Sickle Cell Disease: Establishing a Molecular Framework for Delayed Union in a Nigerian Cohort

Delayed union and non-union are disproportionately prevalent in patients with sickle cell disease (SCD) undergoing fracture management, yet the molecular mechanisms underlying impaired bone healing in this population remain poorly defined. This study uses RNA sequencing (RNA-seq) transcriptomic profiling to characterise the differential gene expression landscape in fracture haematoma and callus tissue from SCD patients compared to matched controls at Lagos University Teaching Hospital (LUTH) and University of Nigeria Teaching Hospital (UNTH), Enugu. Twenty SCD patients and twenty demographically matched controls will undergo standardised callus biopsy at six weeks post-fracture. RNA-seq data will be analysed for differentially expressed genes using DESeq2, followed by gene ontology enrichment, pathway analysis, and integration with published bone healing molecular networks. Protein validation of key candidates will be performed using Western blot and immunohistochemistry. The study will identify specific molecular pathways, including HIF-1-alpha signalling, Wnt/beta-catenin axis activity, and VEGF-mediated angiogenesis, that are dysregulated in SCD bone healing. The research hypothesises that SCD fracture callus demonstrates a fundamentally different transcriptomic signature characterised by suppressed osteogenic differentiation and enhanced inflammatory signalling, establishing a new molecular framework for non-union in SCD. Findings will generate publishable molecular targets for potential therapeutic intervention and contribute an original theoretical model to the African orthopaedic research canon. Keywords: sickle cell disease, transcriptomics, bone healing, delayed union, RNA sequencing.