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bioRxiv · 10.1101/778126

Prostaglandin D2 Signaling is Not Involved in Rat Hindlimb Tendon Healing

Sarver, D. C.·Sugg, K. B.·Talarek, J. R.·Swanson, J. B.·Oliver, D. J.·Hinken, A. C.·Kramer, H. F.·Mendias, C. L.
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Abstract

Injured tendons heal through the formation of a fibrovascular scar that has inferior mechanical properties compared to native tendon tissue. Reducing inflammation that occurs as a result of the injury could limit scar formation and improve functional recovery of tendons. Prostaglandin D2 (PGD2) plays an important role in promoting inflammation in some injury responses and chronic disease processes, and the inhibition of PGD2 has improved healing and reduced disease burden in animal models and early clinical trials. Based on these findings, we sought to determine the role of PGD2 signaling in the healing of injured tendon tissue. We tested the hypothesis that a potent and specific inhibitor of hematopoietic PGD synthase (HPGDS), GSK2894631A, would improve the recovery of tendons of adult male rats following an acute tenotomy and repair. To test this hypothesis, we performed a full-thickness plantaris tendon tenotomy followed by immediate repair and treated rats twice daily with either 0mg/kg, 2mg/kg, or 6mg/kg of GSK2894631A. Tendons were collected either 7 or 21 days after surgical repair, and mechanical properties of tendons were assessed along with RNA sequencing and histology. While there were some differences in gene expression across groups, the targeted inhibition of HPGDS did not impact the functional repair of tendons after injury as HPGDS expression was surprisingly low in injured tendons. These results indicate that PGD2 signaling does not appear to be important in modulating the repair of injured tendon tissue.

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Sarver, D. C., Sugg, K. B., Talarek, J. R., Swanson, J. B., Oliver, D. J., Hinken, A. C., Kramer, H. F., Mendias, C. L.. 2019-09-23. Prostaglandin D2 Signaling is Not Involved in Rat Hindlimb Tendon Healing. https://doi.org/10.1101/778126

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