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1.
Connect Tissue Res ; 57(2): 99-112, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26558768

RESUMEN

PURPOSE: Preclinical studies have reported that bone morphogenetic protein (BMP)-2 promotes bone-tendon healing following anterior cruciate ligament reconstruction. We examined the region-specific effects of BMP-2 on osteoblast and fibroblast differentiation in a highly standardized murine in vitro co-culture model of bone-tendon integration. MATERIALS AND METHODS: We used quantitative PCR to measure the dose- and time-dependent influence of BMP-2 on the expression of alkaline phosphatase, osteocalcin, collagen type 1 (alpha 1 chain), runt-related transcription factor 2, osteopontin, collagen type 1 (alpha 2 chain), collagen type 5 (alpha 1 chain), decorin, fibromodulin, mohawk homeobox, bone morphogenetic protein receptor, type 1A, bone morphogenetic protein receptor, type 2, and Noggin in the osteoblast, interface, and fibroblast regions of a co-culture model of the murine preosteoblast cell line MC3T3-E1 and the fibroblast cell line 3T6. RESULTS: Stimulation with BMP-2 resulted in a significant upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), collagens (p < 0.001), runt-related transcription factor 2 (p < 0.05), and osteopontin (p < 0.001) expression in the osteoblast region. In the interface region, BMP-2 exposure led to dose- and time-dependent upregulation of alkaline phosphatase (p < 0.001), osteocalcin (p < 0.001), osteopontin (p < 0.001), runt-related transcription factor 2 (p < 0.001), and markers of extracellular matrix production (p < 0.001). Both BMP receptors showed a significant BMP-2-dependent upregulation at the interface region, and Noggin was downregulated at the osteoblast and interface region following BMP-2 exposure. CONCLUSIONS: Exposure to BMP-2 upregulated the expression of genes associated with bone-tendon integration in vitro, suggesting the stimulation of transdifferentiation processes at the interface and fibroblast regions as well as the induction of positive feedback mechanisms. Further studies will be needed to establish BMP-2 dose and treatment algorithms following tendon reinsertion and reconstruction.


Asunto(s)
Proteína Morfogenética Ósea 2/farmacología , Huesos/fisiología , Oseointegración/efectos de los fármacos , Tendones/fisiología , Animales , Huesos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Técnicas de Cocultivo , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Retroalimentación Fisiológica/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Tendones/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
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