노인성 근감소증에서 부갑상선 호르몬 유사체 효능 연구 = Teriparatide Has a Protective Role in Aging-induced Sarcopenia by Stabilizing the Neuromuscular Junction

다국어 초록 (Multilingual Abstract)

Traditionally known for its effects on bone and kidney metabolism, parathyroid hormone has recently been highlighted for its broader role in musculoskeletal health, partiㅊularly its effects on skeletal muscle. However, little is known about the role and mechanism of teriparatide in skeletal muscle. Thus, I hypothesized that teriparatide would have a positive effect on sarcopenia in the elderly.

In a retrospective longitudinal study, I retrospectively compared the cross-sectional area (CSA) of the psoas major, iliopsoas, and rectus femoris on CT scans in osteoporosis patients who received teriparatide treatment. For further investigation, aged female C57BL/6 mice (22-month-old) were treated with teriparatide via intraperitoneal injections for two months, and then hind-limb muscles were collected for analysis. C2C12 cell line (myoblast cells) experiments were set up to confirm the expression results obtained in vivo.

There was an increase in cross-sectional area across muscles observed after teriparatide treatment compared with before treatment. When teriparatide was injected into aged mice, the expression of PTH1R in the skeletal muscle was confirmed to be dramatically increased compared to the control. Furthermore, teriparatide treatment increased muscle fiber CSA and muscle contractility in aged mice, and its action was associated with mTOR signaling. To determine how teriparatide experts positive effects on muscle, I performed transcriptome analysis in muscle and confirmed that teriparatide affects the neuromuscular junction. Consistent with these in vivo results, I found that teriparatide treatment of C2C12 cells increased the expression of acetylcholine receptor clusters in myocytes and increased myotube size.

These findings highlight the therapeutic potential of teriparatide not only in bone or mineral disorders but also as a novel strategy to counteract sarcopenia and neuromuscular degeneration, particularly in aging.

목차 (Table of Contents)

• ACKNOWLEDGEMENTS ii
• ABBREVIATIONS iv
• LIST OF FIGURES v
• LIST OF TABLES vi
• ABSTRACT 1
• INTRODUCTION 3
• MATERIALS AND METHODS 11
• RESULTS 19
• DISCUSSION 30
• REFERENCES 40
• FIGURES 54
• TABLES 67
• KOREAN ABSTRACT 71