Elysse Orchard1, Wanda Green2, Renjith Parameswaran Nair3, Fleurette Abreo4 and Gulshan Sunavala-Dossabhoy3*
1Department of Animal Resources, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA
2Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA
3Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA
4Department of Pathology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA
Bone is a unique tissue that has the ability to repair itself and return to full function. Bone regeneration is a well-synchronized biological process that recapitulates embryonic bone development. The establishment of a functional vascular supply has been shown to be essential for proper ossification of newly deposited one, and impaired angiogenesis as in advanced age, diabetes, and anti-cancer treatments affects bone repair. Endothelial guanosine 3', 5'-cyclic monophosphate (cGMP) is known to support angiogenesis, and sildenafil, a phosphodiesterase 5 (PDE5) antagonist, prevents cGMP hydrolysis and promotes the formation of new blood vessels. Since the development of functional vascular networks is critical to bone repair, we investigated the effects of sildenafil on early alveolar bone regeneration following exodontia. Our results demonstrate that per-oral administration of sildenafil (10 mg/kg/day) in rats delays the dissolution and replacement of the sanguine clot with granulation tissue. As a result, the number of replicating cells, a hallmark of regenerating tissue, observed on day 4 is remarkably lower in sildenafil-treated animals than their control counterparts (control: mean±SD, 47.35 ± 9.21; sildenafil: mean±SD, 11.47 ± 5.14). Similarly, cells expressing transcription factor Cbfa-1/Runx2 and osteopontin, markers of differentiating osteoblasts, were fewer in treated animals (control: mean±SD, 83.18 ± 4.60; sildenafil: mean±SD, 13.77 ± 4.63). Treatment with hydrolysis-resistant cyclic GMP (cGMP) showed findings similar to sildenafiltreated animals suggesting the negative impact of cGMP on early inflammatory phase of bone healing. Nevertheless, histological differences were not significant between the 2 groups on day 8. Based on these findings, we conclude that sildenafil transiently retards early events in alveolar bone healing.
PDE5, cGMP, Bone regeneration
Orchard E, Green W, Nair RP, Abreo F, Sunavala-Dossabhoy G. Sildenafil Transiently Delays Early Alveolar Bone Healing of Tooth Extraction Sockets. Clin Surg. 2017; 2: 1458.