M-W Dai1, J-G Chu2, F-M Tian3, H-P Song4, Y Wang5, Y-Z Zhang6, L Zhang7. 1. Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: daimuwei@hotmail.com. 2. Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: 2589469936@qq.com. 3. Medical Research Center, North China University of Science and Technology, Tangshan, China. Electronic address: tfm9911316@163.com. 4. Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China. Electronic address: songhuiping@163.com. 5. Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China. Electronic address: 93421679@qq.com. 6. Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: yingze1953@163.com. 7. Department of Orthopedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China; Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China. Electronic address: zhliu130@sohu.com.
Abstract
OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 μg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.
OBJECTIVE: To evaluate the effects of PTH(1-34) on cartilage, subchondral bone mass and structure in medial meniscectomized guinea pigs and compare them to those of celecoxib (CLX). METHOD: Forty-eight 3-month-old male Hartley albino guinea pigs received either sham or medial meniscectomy (MNX) operations. One week after the procedure, meniscectomized animals began 12 weeks of treatment by oral administration of CLX (20 mg/kg, daily), subcutaneous injection of PTH (1-34) (24 μg/kg, 5 days/week), or normal saline for MNX group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. RESULTS: OARSI scores indicated cartilage degeneration was partially inhibited by either CLX or PTH(1-34). Cartilage was significantly thicker in PTH(1-34)-treated animals than in CLX-treated animals. Both CLX and PTH(1-34) treatment were associated with lower ADAMTS-4 and periostin expression than MNX. MMP-13 expression in PTH(1-34) group was significantly lower than that in CLX group. However, AGG expression and the ratio of Col-II/MMP-13 expression in PTH(1-34) group were significantly higher than in the CLX group. Micro-CT analysis showed BMD, BV/TV, and Tb.Th levels to be significantly lower in the MNX group and CLX groups than in the sham group, but these parameters were significantly higher in the PTH(1-34) group than in either the MNX group or CLX group. CONCLUSIONS: Both CLX and PTH(1-34) exhibits protective effects on cartilage degeneration in meniscectomized guinea pigs. However, PTH(1-34) exhibited superior performance to CLX not only in metabolism of cartilage tissue but also in maintenance of subchondral bone micro-architecture.
Authors: Ufuk Tan Timur; Marjolein M J Caron; Ralph M Jeuken; Yvonne M Bastiaansen-Jenniskens; Tim J M Welting; Lodewijk W van Rhijn; Gerjo J V M van Osch; Pieter J Emans Journal: Int J Mol Sci Date: 2020-09-22 Impact factor: 5.923
Authors: Graham R Williams; J H Duncan Bassett; Natalie C Butterfield; Katherine F Curry; Julia Steinberg; Hannah Dewhurst; Davide Komla-Ebri; Naila S Mannan; Anne-Tounsia Adoum; Victoria D Leitch; John G Logan; Julian A Waung; Elena Ghirardello; Lorraine Southam; Scott E Youlten; J Mark Wilkinson; Elizabeth A McAninch; Valerie E Vancollie; Fiona Kussy; Jacqueline K White; Christopher J Lelliott; David J Adams; Richard Jacques; Antonio C Bianco; Alan Boyde; Eleftheria Zeggini; Peter I Croucher Journal: Nat Commun Date: 2021-01-20 Impact factor: 17.694