Journal of Inflammation Research (Feb 2023)
Investigation of the Underlying Mechanism of Sclerosteosis Expression in Muscle Tissue in Multiple Myeloma with Sarcopenia
Abstract
Jie Ren,1,* Jingzhou Wang,2,* Xingchen Yao,1 Yue Wu,1 Ming Shi,1 Xiangjun Shi,3 Xinru Du1 1Department of Orthopaedics, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China; 2Department of Orthopaedics, Beijing Daxing District People’s Hospital, Beijing, 102600, People’s Republic of China; 3Department of Hematology, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinru Du, Department of orthopaedics, Beijing Chao-yang Hospital, No. 8 of Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 13683156652, Email [email protected]: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia.Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry.Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG.Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.Keywords: multiple myeloma, SOST, multiple myeloma mouse model, ethology, sarcopenia, myoblast differentiation
