K A Elsaid1, L Zhang2, Z Shaman3, C Patel3, T A Schmidt4, G D Jay2. 1. Department of Pharmaceutical Sciences, MCPHS University, Boston, MA 02115, USA. Electronic address: Khaled.elsaid@mcphs.edu. 2. Department of Emergency Medicine, Rhode Island Hospital, Providence, RI 02903, USA. 3. Department of Pharmaceutical Sciences, MCPHS University, Boston, MA 02115, USA. 4. Faculty of Kinesiology and Schulich School of Engineering, University of Calgary, Canada.
Abstract
OBJECTIVE: Study the impact of intra-articular interleukin-1 receptor antagonist (IL-1 ra) treatment on lubricin biosynthesis following anterior cruciate ligament transection (ACLT) in the rat and evaluate the effect of combined IL-1 ra and recombinant human lubricin (rhPRG4) treatments on chondrocyte apoptosis. METHODS: ACLT was performed in male Lewis rats. Treatments included IL-1 ra or vehicle (n = 36 in each group). IL-1 ra intra-articular dosing was performed on days 1, 3, 5 and 7 following ACLT using Anakinra (150 mg/ml; 40 μl). At 3 and 5 weeks, animals were sacrificed and RNA was isolated. Histological analyses included Safranin O and H&E. Lubricin synovial fluid (SF) lavage concentrations were determined at 5 weeks. ACLT animals were treated with a single injection of vehicle, IL-1 ra (75 mg/ml; 40 μl), rhPRG4 (200 μg/ml; 40 μl), or IL-1 ra + rhPRG4 (75 mg/ml + 200 μg/ml; 40 μl) (n = 6 in each group) on day 7 following ACLT and cartilage was probed for cleaved caspase-3 at 5 weeks. RESULTS: IL-1 ra treatment improved lubricin expression (P < 0.001) and lubricin SF lavage concentrations in the IL-1 ra group was higher (P = 0.005) than the vehicle. IL-1 ra treatment reduced cartilage and synovial scores (P < 0.001) compared to vehicle. IL-1 ra and rhPRG4 acted synergistically to reduce caspase-3 positive chondrocytes (P < 0.001) compared to individual treatments. CONCLUSION: IL-1 ra treatment preserved lubricin following ACLT and a combined treatment of IL-1 ra + rhPRG4 may act synergistically to reduce cartilage catabolism.
OBJECTIVE: Study the impact of intra-articularinterleukin-1 receptor antagonist (IL-1 ra) treatment on lubricin biosynthesis following anterior cruciate ligament transection (ACLT) in the rat and evaluate the effect of combined IL-1 ra and recombinant humanlubricin (rhPRG4) treatments on chondrocyte apoptosis. METHODS: ACLT was performed in male Lewis rats. Treatments included IL-1 ra or vehicle (n = 36 in each group). IL-1ra intra-articular dosing was performed on days 1, 3, 5 and 7 following ACLT using Anakinra (150 mg/ml; 40 μl). At 3 and 5 weeks, animals were sacrificed and RNA was isolated. Histological analyses included Safranin O and H&E. Lubricin synovial fluid (SF) lavage concentrations were determined at 5 weeks. ACLT animals were treated with a single injection of vehicle, IL-1 ra (75 mg/ml; 40 μl), rhPRG4 (200 μg/ml; 40 μl), or IL-1 ra + rhPRG4 (75 mg/ml + 200 μg/ml; 40 μl) (n = 6 in each group) on day 7 following ACLT and cartilage was probed for cleaved caspase-3 at 5 weeks. RESULTS:IL-1 ra treatment improved lubricinexpression (P < 0.001) and lubricin SF lavage concentrations in the IL-1 ra group was higher (P = 0.005) than the vehicle. IL-1 ra treatment reduced cartilage and synovial scores (P < 0.001) compared to vehicle. IL-1 ra and rhPRG4 acted synergistically to reduce caspase-3 positive chondrocytes (P < 0.001) compared to individual treatments. CONCLUSION:IL-1 ra treatment preserved lubricin following ACLT and a combined treatment of IL-1 ra + rhPRG4 may act synergistically to reduce cartilage catabolism.
Authors: Virginia B Kraus; Janet L Huebner; Christian Fink; Jeffrey B King; Spencer Brown; T Parker Vail; Farshid Guilak Journal: Arthritis Rheum Date: 2002-02
Authors: B J Heard; N M Solbak; Y Achari; M Chung; D A Hart; N G Shrive; C B Frank Journal: Osteoarthritis Cartilage Date: 2013-09-05 Impact factor: 6.576
Authors: Kimberly A Waller; Ling X Zhang; Khaled A Elsaid; Braden C Fleming; Matthew L Warman; Gregory D Jay Journal: Proc Natl Acad Sci U S A Date: 2013-03-25 Impact factor: 11.205
Authors: Michael L Samsom; Sheila Morrison; Nemanja Masala; Benjamin D Sullivan; David A Sullivan; Heather Sheardown; Tannin A Schmidt Journal: Exp Eye Res Date: 2014-07-02 Impact factor: 3.467
Authors: Carl R Flannery; Richard Zollner; Chris Corcoran; Aled R Jones; Adam Root; Moisés A Rivera-Bermúdez; Tracey Blanchet; Jason P Gleghorn; Lawrence J Bonassar; Alison M Bendele; Elisabeth A Morris; Sonya S Glasson Journal: Arthritis Rheum Date: 2009-03
Authors: Katherine M Larson; Ling Zhang; Khaled A Elsaid; Tannin A Schmidt; Braden C Fleming; Gary J Badger; Gregory D Jay Journal: J Orthop Res Date: 2017-03-02 Impact factor: 3.494
Authors: Kimberly A Waller; Kaitlyn E Chin; Gregory D Jay; Ling X Zhang; Erin Teeple; Scott McAllister; Gary J Badger; Tannin A Schmidt; Braden C Fleming Journal: Am J Sports Med Date: 2017-01-27 Impact factor: 6.202
Authors: Jonah I Donnenfield; Naga Padmini Karamchedu; Braden C Fleming; Janine Molino; Benedikt L Proffen; Martha M Murray Journal: Am J Transl Res Date: 2022-03-15 Impact factor: 4.060
Authors: Brendan L Roach; Arta Kelmendi-Doko; Elaine C Balutis; Kacey G Marra; Gerard A Ateshian; Clark T Hung Journal: Tissue Eng Part A Date: 2016-03-31 Impact factor: 3.845
Authors: Adrianne Stone; Matthew W Grol; Merry Z C Ruan; Brian Dawson; Yuqing Chen; Ming-Ming Jiang; I-Wen Song; Prathap Jayaram; Racel Cela; Francis Gannon; Brendan H L Lee Journal: Hum Gene Ther Date: 2018-10-17 Impact factor: 5.695
Authors: Rachael S Watson Levings; Andrew D Smith; Ted A Broome; Brett L Rice; Eric P Gibbs; David A Myara; E Viktoria Hyddmark; Elham Nasri; Ali Zarezadeh; Padraic P Levings; Yuan Lu; Margaret E White; E Anthony Dacanay; Gregory B Foremny; Christopher H Evans; Alison J Morton; Mathew Winter; Michael J Dark; David M Nickerson; Patrick T Colahan; Steven C Ghivizzani Journal: Hum Gene Ther Clin Dev Date: 2018-06 Impact factor: 5.032