Bone Morphogenetic Protein 2 Is Involved In The Proliferation And Collagen Synthesis Of Human Hyperplastic Scar Fibroblasts

Hypertrophic scar (HS) is a major skin fibrotic disorder characterized by excessive cell proliferation and deposition of extracellular matrix (ECM) components, particularly type I collagen. The purpose of the present study was to investigate the effect of bone morphogenetic protein 2 (BMP-2) on proliferation and collagen synthesis in human hypertrophic scar fibroblasts. HS and normal skin (NS) tissues were obtained from patients who underwent HS surgical excision. Fibroblasts were isolated from the HS and NS tissues. The expression of BMP-2 in HS tissues and HS fibroblasts was determined by immunohistochemistry, western blot and reverse transcription polymerase chain reaction (RT-RCR). Fully human BMP-2 phosphorothioated single-stranded antisense oligonucleotides (asODN) transfection was conducted to explore the effect of BMP-2 on the proliferation of fibroblasts. Collagen synthesis was estimated with hydroxyproline colorimetry. It was observed that BMP-2 expression was significantly increased in the epidermis and dermis of HS tissue, especially in the fibroblasts and mesenchyme of dermis, as compared to that in NS preparations. The proliferation of HS fibroblasts was significantly decreased by knockdown of BMP-2 expression with BMP-2-asODN. BMP-2-asODN transfection also led to a significant reduction in type I collagen synthesis in HS fibroblasts. These data suggested that BMP-2 might play an important role in hypertrophic scar formation, and provide a molecular basis for new therapeutic strategies to reducing traumatic and post-surgical scarring by targeting BMP-2 and/or related pathways.