Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

Bone and Joint Research - Tập 6 Số 2 - Trang 90-97 - 2017
Rebecca Rajfer1, A. Kılıç2, Andrew S. Neviaser1, Leah M. Schulte1, Su M Hlaing3, Jose Landeros3, Mónica G. Ferrini3, Edward Ebramzadeh4, So Hyun Park4
1Department of Orthopaedic Surgery, George Washington University, Washington, DC, USA
2Department of Orthopaedics, School of Medicine, Bahcesehir University, Istanbul, Turkey.
3Department of Health and Life Sciences, College of Science and Health, Charles Drew University of Medicine and Science, Los Angeles, California, USA
4Department of Orthopaedic Surgery, The J. Vernon Luck, Sr., M.D. Orthopaedic Research Center, Orthopaedic Institute for Children, University of California, Los Angeles, California, USA

Tóm tắt

ObjectivesWe investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days.Materials and MethodsUnilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry.ResultsWhen compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42.ConclusionThis study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2.

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Bone and Joint Research

Tập 6 Số 2

90-97

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