J Temp1, D Labuz2, R Negrete3, V Sunkara4, H Machelska5. 1. Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany. Electronic address: julia.temp@charite.de. 2. Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany. Electronic address: dominika.labuz@charite.de. 3. Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany. Electronic address: roger.negrete@charite.de. 4. Department of Mathematics and Computer Science, Freie Universität Berlin, Germany; Computational Medicine, Zuse Institute Berlin, Germany. Electronic address: sunkara@mi.fu-berlin.de. 5. Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Berlin, Germany. Electronic address: halina.machelska@charite.de.
Abstract
OBJECTIVE: To investigate sex effects on pain-related behaviors in the medial meniscal transection (MMT) knee osteoarthritis (OA) model. METHODS: Experiments were performed in male and female C57BL/6J mice (12/group/sex). MMT was induced by transection of the medial collateral ligament and the medial meniscus. Sham-operated and naïve mice served as controls. Mechanical and heat sensitivity in hind paws, hind limb use, and locomotor activity were measured for 3 months. Knee histology was performed on week 12. RESULTS: In males, MMT triggered a bi-phasic mechanical hypersensitivity and decreased load on OA limb, with an acute post-operative (1-5 days) and chronic (3-12 weeks) OA phases separated by a remission in the intermediate phase (1-2 weeks). Females showed a less pronounced bi-phasic pattern, with a greater mechanical hypersensitivity, but not poorer limb use, than males in the intermediate phase (maximal difference: 1.1 g, 95% confidence intervals (CI) [0.7, 1.5]). There were no major sex differences in the chronic phase. MMT did not induce heat hypersensitivity or change in locomotor activity in the chronic phase in both sexes. MMT caused more severe cartilage damage in males than in females (maximal difference: 1.1 score points, 95% CI [1.9, 0.3]), and a comparable between sexes osteophyte formation. The knee damage did not correlate with pain. CONCLUSIONS: MMT modelled human knee OA well, capturing cartilage destruction and osteophyte formation, mechanical pain, and poorer limb use in both sexes. Sex differences in pain were modality- and time-dependent, reflecting complex sex-related features of human OA.
OBJECTIVE: To investigate sex effects on pain-related behaviors in the medial meniscal transection (MMT) knee osteoarthritis (OA) model. METHODS: Experiments were performed in male and female C57BL/6J mice (12/group/sex). MMT was induced by transection of the medial collateral ligament and the medial meniscus. Sham-operated and naïve mice served as controls. Mechanical and heat sensitivity in hind paws, hind limb use, and locomotor activity were measured for 3 months. Knee histology was performed on week 12. RESULTS: In males, MMT triggered a bi-phasic mechanical hypersensitivity and decreased load on OA limb, with an acute post-operative (1-5 days) and chronic (3-12 weeks) OA phases separated by a remission in the intermediate phase (1-2 weeks). Females showed a less pronounced bi-phasic pattern, with a greater mechanical hypersensitivity, but not poorer limb use, than males in the intermediate phase (maximal difference: 1.1 g, 95% confidence intervals (CI) [0.7, 1.5]). There were no major sex differences in the chronic phase. MMT did not induce heat hypersensitivity or change in locomotor activity in the chronic phase in both sexes. MMT caused more severe cartilage damage in males than in females (maximal difference: 1.1 score points, 95% CI [1.9, 0.3]), and a comparable between sexes osteophyte formation. The knee damage did not correlate with pain. CONCLUSIONS: MMT modelled human knee OA well, capturing cartilage destruction and osteophyte formation, mechanical pain, and poorer limb use in both sexes. Sex differences in pain were modality- and time-dependent, reflecting complex sex-related features of humanOA.
Authors: Yuyan Wang; Emma S Wagner; Danqiao Yu; Kevin J Chen; Taidhgin J Keel; Sarah L Pownder; Matthew F Koff; Jonathan Cheetham; Kirk J Samaroo; Heidi L Reesink Journal: J Orthop Res Date: 2022-01-07 Impact factor: 3.102
Authors: Lixia Zhang; Cameron L Kirkwood; Jiho Sohn; Ashley Lau; Mary Bayers-Thering; Supinder Kour Bali; Sridhar Rachala; John M Marzo; Mark J Anders; Frank Beier; Keith L Kirkwood Journal: Arthritis Res Ther Date: 2021-11-16 Impact factor: 5.156
Authors: I M Berke; E Jain; B Yavuz; T McGrath; L Chen; M J Silva; G Mbalaviele; F Guilak; D L Kaplan; L A Setton Journal: Osteoarthritis Cartilage Date: 2020-11-24 Impact factor: 6.576