Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model  

作　　者：R.Nicole Howie Samuel Herberg Emily Durham Zachary Grey Grace Bennfors Mohammed Elsalanty Amanda C.LaRue William D.Hill James J.Cray 

机构地区：[1]Oral Health Sciences,Medical University of South Carolina,Charleston,SC,USA [2]Biomedical Engineering,Case Western Reserve University,Cleveland,OH,USA [3]Cellular Biology and Anatomy,Augusta University,Augusta,GA,USA [4]Oral Biology,Augusta University,Augusta,GA,USA [5]Orthopaedic Surgery,Augusta University,Augusta,GA,USA [6]Pathology and Laboratory Medicine,Medical University of South Carolina,Charleston,SC,USA [7]Institute for Regenerative and Reparative Medicine,Augusta University,Augusta,GA,USA [8]Research Service of the Ralph H Johnson VA Medical Center,Charleston,SC,USA [9]Charlie Norwood VA Medical Center,Augusta,GA,USA [10]Department of Regenerative Medicine and Cellular Biology,Charleston,SC,USA [11]Wake Forest Institute for Regenerative Medicine,Wake Forest School of Medicine,Winston-Salem,NC,USA [12]Division of Anatomy,College of Medicine,Ohio State University,Columbus,OH,USA

出　　处：《International Journal of Oral Science》2018年第4期212-222,共11页国际口腔科学杂志（英文版）

基　　金：supported by a grant from the Musculoskeletal Transplant Foundation (JC);the National Institute of Health, the National Institute of Aging [NIH-NIA PO1-AG036675] (ME, WDH);in part by the Department of Veterans Affairs (VA Merit Award BX000333, ACL; 1I01CX000930-01, WDH);funded through a training grant from the National Institutes of Health National Institute of Dental and Craniofacial Research [5T32DE017551];S.H. is funded through a fellowship from the National Institutes of Health National Institute of Dental and Craniofacial Research [5F32DE02471202];supported by the National Institutes of Health National Institute of General Medicine [P30GM103331]

摘　　要：Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients' ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg^(-1) sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

关 键 词：Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model 

分 类 号：R[医药卫生]