Bing'er Xu1, Yuting He1, Yi Lu1, Weiying Ren1, Jiping Shen1, Kefen Wu1, Kan Xu1, Jiayu Wu1, Yu Hu2. 1. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China. 2. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Center for Evidence Based Medicine and Clinical Epidemiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: hu.yu@zs-hospital.sh.cn.
Abstract
AIMS: In this study, we evaluate the effects of glucagon-like peptide 2 (GLP-2) on bone microarchitecture, bone turnover markers (BTMs) and inflammation markers in ovariectomized (OVX) rats. MATERIAL AND METHODS: In total, 31 Sprague-Dawley rats were divided into the following three groups: sham (control sham-operated with vehicle, n = 7), OV (OVX with vehicle, n = 12), and GLP-2 (OVX with GLP-2, n = 12). Intervention began at the 12th week after surgery and lasted for 4 weeks. The dosage of the GLP-2 was 160 μg/kg/d through subcutaneous injections, and normal saline was used as the vehicle agent. After 4 weeks of treatment, serum BTM and inflammation marker levels were measured by ELISA, and femora samples were analyzed by qRT-PCR, micro-CT, histology and histomorphometry. KEY FINDINGS: After 4 weeks of treatment, serum TRAcP-5b and RANKL levels as well as the CTX-1/P1NP ratio in the GLP-2 group decreased, and ALP activity, P1NP level, and OPG/RANKL ratio increased significantly; qRT-PCR analysis showed that mRNA levels of RANKL decreased, and Runx2, ALP, and Col-1 levels as well as the OPG/RANKL ratio increased significantly in the GLP-2 group compared with the OV group. In bone histology analysis, GLP-2 significantly decreased the AV/MV, Oc.N and Oc.S but increased the Ob.N, BFR and MAR. Analysis with μ-CT showed that the BMD, BV/TV, Tb.N and Conn.D increased significantly in the GLP-2 group compared with the OV group. The levels of serum inflammation markers TNF-α, IL-1β and IL-6 decreased, and TGF-β levels increased in the GLP-2 group compared with the OV group. SIGNIFICANCE: GLP-2 may have a positive impact on osteoporosis by promoting bone formation, inhibiting bone resorption and decreasing circulatory inflammation in ovariectomized rats.
AIMS: In this study, we evaluate the effects of glucagon-like peptide 2 (GLP-2) on bone microarchitecture, bone turnover markers (BTMs) and inflammation markers in ovariectomized (OVX) rats. MATERIAL AND METHODS: In total, 31 Sprague-Dawley rats were divided into the following three groups: sham (control sham-operated with vehicle, n = 7), OV (OVX with vehicle, n = 12), and GLP-2 (OVX with GLP-2, n = 12). Intervention began at the 12th week after surgery and lasted for 4 weeks. The dosage of the GLP-2 was 160 μg/kg/d through subcutaneous injections, and normal saline was used as the vehicle agent. After 4 weeks of treatment, serum BTM and inflammation marker levels were measured by ELISA, and femora samples were analyzed by qRT-PCR, micro-CT, histology and histomorphometry. KEY FINDINGS: After 4 weeks of treatment, serum TRAcP-5b and RANKL levels as well as the CTX-1/P1NP ratio in the GLP-2 group decreased, and ALP activity, P1NP level, and OPG/RANKL ratio increased significantly; qRT-PCR analysis showed that mRNA levels of RANKL decreased, and Runx2, ALP, and Col-1 levels as well as the OPG/RANKL ratio increased significantly in the GLP-2 group compared with the OV group. In bone histology analysis, GLP-2 significantly decreased the AV/MV, Oc.N and Oc.S but increased the Ob.N, BFR and MAR. Analysis with μ-CT showed that the BMD, BV/TV, Tb.N and Conn.D increased significantly in the GLP-2 group compared with the OV group. The levels of serum inflammation markers TNF-α, IL-1β and IL-6 decreased, and TGF-β levels increased in the GLP-2 group compared with the OV group. SIGNIFICANCE: GLP-2 may have a positive impact on osteoporosis by promoting bone formation, inhibiting bone resorption and decreasing circulatory inflammation in ovariectomized rats.
Authors: Ke Sui; Kevin M Tveter; Fiona G Bawagan; Patricia Buckendahl; Savannah A Martinez; Zehra H Jaffri; Avery T MacDonell; Yue Wu; Rocio M Duran; Sue A Shapses; Diana E Roopchand Journal: Front Pharmacol Date: 2022-06-21 Impact factor: 5.988
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