title: Effect of indomethacin and lactoferrin on human tenocyte proliferation and collagen formation in vitro.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with injuries and inflammation of tendon and ligament, and as post-surgical analgesics. The aim of this study is to investigate the effect of indomethacin, a classic NSAID and its combinational effect with an anabolic agent of skeletal tissue, lactoferrin, on the proliferation and collagen formation of human tenocytes in vitro. A factorial experimental design was employed to study the dose-dependent effect of the combination of indomethacin and lactoferrin. The results showed that indomethacin at high concentration (100 μM) inhibited human tenocyte proliferation in culture medium with 1-10% fetal bovine serum (FBS) in vitro. Also, high dose of indomethacin inhibited the collagen formation of human tenocytes in 1% FBS culture medium. Lactoferrin at 50-100 μg/ml promoted human tenocyte survival in serum-free culture medium and enhanced proliferation and collagen synthesis of human tenocytes in 1% FBS culture medium. When 50-100 μg/ml lactoferrin was used in combination with 100-200 μM indomethacin, it partially rescued the inhibitory effects of indomethacin on human tenocyte proliferation, viability and collagen formation. To our knowledge, it is the first evidence that lactoferrin is anabolic to human tenocytes in vitro and reverses potential inhibitory effects of NSAIDs on human tenocytes.
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP; Department of Orthopaedic, Beijing Hospital of Ministry of Public Health, Beijing, China 100730.
authors.forename: Yaonan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carr
authors.affiliation: Centre for Nanohealth, College of Medicine, Swansea University, Singleton Park, Swansea, UK SA2 8PP. Electronic address: z.xia@swansea.ac.uk.
authors.forename: Zhidao
authors.initials: Z
authors.lastname: Xia
mesh_terms: D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D004338:Drug Combinations; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D013710:Tendons / Q000166:cytology* / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D003094:Collagen; D007781:Lactoferrin; D007213:Indomethacin
keywords: Anabolic; Human tenocyte; Indomethacin; Lactoferrin; Non-steroidal anti-inflammatory drugs (NSAIDs)