Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics

Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

Molecular MRI Images of the Transplanted Human Mesenchymal Stem Cells in the Liver, Kidney, Bladder and Penile Cavernosum of Rats / 대한비뇨기과학회지

PURPOSE: Molecular magnetic resonance (MR) imaging techniques using superparamagnetic iron oxide nanocrystals (SPIO) have been developed for noninvasively monitoring stem cells. This study was performed to investigate if the presence of transplanted human mesenchymal stem cells in the liver, kidney, bladder and penile cavernosum can be evaluated noninvasively with using molecular MR imaging. MATERIALS AND METHODS: SPIO (Feridex; AMI, Cambridge, USA) were transferred to the human mesenchymal stem cells (hMSCs) using GenePORTER. The labeling viability, efficiency and differentiation of the SPIO transferred hMSCs were examined with Tripan blue, Von Kossa, alkaline phosphatase, toluidine blue, oil red O and Prussian blue staining. The SPIO labelled hMSCs were transplanted to the liver, kidney, bladder and penile cavernosum of rats, and the MR images were examined in vitro or in vivo using 1.5 T MR. RESULTS: The viability and efficiency of the SPIO transferred hMSCs were good. Osteogenic, chondrogenic or adipogenic differentiation from the SPIO transferred hMSCs was observed. A decrease of the MR signal intensity of the SPIO transferred hMSCs with using GenePORTER was found in vitro. A decrease of the MR signal intensity was found at concentrations that were more than 1x10(5) hMSCs in vitro. The MR signal intensity at the areas of the SPIO transferred hMSCs decreased in the liver, kidney, bladder and penile cavernosum. The intracellular SPIOs were confirmed in the SPIO labelled hMSCs that were transplanted in the liver, kidney, bladder and penile cavernosum with Prussian blue staining. CONCLUSIONS: The SPIO labelled hMSCs in the liver, kidney, bladder and penis can be evaluated noninvasively by using molecular MRI.

Increased Serum Concentration of Monocyte Chemoattractant Protein-1 in Systemic Lupus Erythematosus Patients with Antiphospholipid Syndrome / 대한류마티스학회지

OBJECTIVE: To determine the association of serum monocyte chemoattractant protein-1 (MCP-1) concentration and clinical variables of antiphospholipid syndrome (APS). METHODS: We investigated the serum concentration of MCP-1 in systemic lupus erythematosus (SLE) patients by ELISA. The clinical features of APS were evaluated in SLE patients, and anticardiolipin antibody (aCL) was determined at the time of blood sampling. RESULTS: Serum MCP-1 levels (median [range]) in 76 SLE patients were significantly higher than those in 99 healthy controls (192 pg/ml [116, 560] versus 91 pg/ml [26~251], p3 years) had higher levels of MCP-1 than those without (263 pg/ml [166,534] versus 196 pg/ml [116,322], P=0.023). Furthermore, serum MCP-1 levels correlated well with IgG aCL titers (r=0.62, p<0.001). CONCLUSION: Serum MCP-1 levels were elevated in SLE patients, particularly in those with APS, and correlated well with titers of IgG aCL and thrombosis. Our data suggest that increased MCP-1 may play a critical role in the development of APS in SLE patients.