CTLA-4Ig Improves Hyperalgesia in a Mouse Model of Osteoporosis

• Published in: International journal of molecular sciences Vol. 21; no. 24; p. 9479
• Main Authors: Nagao, Nobuto, Wakabayashi, Hiroki, Miyamura, Gaku, Kato, Sho, Naito, Yohei, Sudo, Akihiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.12.2020; MDPI
• Subjects: abatacept; Abatacept - administration & dosage; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Biomedical materials; Bone Density - drug effects; Bone loss; Computed tomography; Cytokines; Cytotoxicity; Disease Models, Animal; Drug withdrawal; Estrogens; Evaluation; Female; Fractures; Gene expression; Hindlimb - cytology; Hindlimb - diagnostic imaging; Hindlimb - drug effects; Hindlimb - pathology; Hyperalgesia; Hyperalgesia - drug therapy; Hyperalgesia - genetics; Hyperalgesia - metabolism; Inflammation; Injections, Intraperitoneal; Lymphocytes; Lymphocytes T; Metabolism; Mice; Oophorectomy; Osteoclasts; Osteoclasts - metabolism; Osteoporosis; Osteoporosis - diagnostic imaging; Osteoporosis - drug therapy; Osteoporosis - genetics; Osteoporosis - metabolism; Ovariectomy; Pain; Pain - drug therapy; Pain - pathology; Pain Measurement; Pain perception; SOST protein; T-Lymphocytes, Cytotoxic - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Wnt protein; Wnt Proteins - genetics; Wnt Proteins - metabolism; X-Ray Microtomography; osteoporosis; pain; abatacept
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21249479

This study aimed to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effects of cytotoxic T lymphocyte-associated antigen-4Ig (CTLA-4Ig) administration in ovariectomized (OVX) mice. Eight-week-old female ddY mice were assigned to three groups: sham-operated mice (SHAM) treated with vehicle, OVX mice treated with vehicle (OVX), and OVX mice treated with CTLA-4Ig (CTLA-4Ig). Vehicle or CTLA-4Ig was injected intraperitoneally, starting immediately after surgery. After 4 weeks of treatment, mechanical sensitivity was examined, and the bilateral hind limbs were removed and evaluated by micro-computed tomography, immunohistochemical analyses, and messenger RNA expression analysis. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs. CTLA-4Ig treatment prevented bone loss in the hindlimbs compared to vehicle administration in the OVX group. Moreover, mechanical hyperalgesia was significantly decreased in the CTLA-4Ig treatment group in comparison to the OVX group. The expression levels of tumor necrosis factor-α (TNF-α) and sclerostin (SOST), as well as the number of osteoclasts, were increased, and the expression level of Wnt-10b was decreased in the OVX group compared with the SHAM group, whereas these parameters were improved in the CTLA-4Ig group compared with the OVX group. The novelty of this research is that CTLA-4Ig administration prevented bone loss and mechanical hyperalgesia induced by ovariectomy in the hindlimbs.