Role of Dkk2 in the Muscle/bone Interaction of Androgen-Deficient Mice

Abstract

Androgen deficiency is known to cause both osteoporosis and sarcopenia. Myokines, humoral factors secreted from the skeletal muscles, have recently been getting attention as the key factors related to the interactions between muscle and bone. Dickkopf (Dkk) 2 is known as an inhibitor of canonical Wnt/β-catenin signaling, and Wnt/β-catenin signaling is crucial for the maintenance of muscle and bone. The present study was therefore performed to investigate the roles of Dkk2 in the alterations of muscle and bone of androgen-deficient mice with orchidectomy (ORX). ORX significantly enhanced Dkk2 mRNA levels, but not other Dkks and secreted frizzled related proteins, in the soleus muscles of mice. Moreover, ORX enhanced serum Dkk2 levels, but not Dkk2 mRNA levels in the tibial bone tissues, the white adipose tissues and liver of mice. In simple regression analyses, serum Dkk2 levels were negatively related to trabecular bone mineral density at the tibias in mice employed in the experiments. In vitro experiments, testosterone suppressed Dkk2 mRNA levels in mouse muscle C2C12 cells. In conclusion, we showed that androgen deficiency enhances Dkk2 expression and secretion in the muscles of mice. Dkk2 might be involved in androgen deficiency-induced muscle wasting and osteopenia as a myokine linking muscle to bone.

Methods and research progress in the construction of animal models of osteosarcopenia: a scoping review

“…This model helps researchers understand the role of androgens, such as testosterone, in the regulation of muscle and bone health and evaluate the efficacy of androgen replacement therapies. Iemura S ( 14 ) show that androgen deficiency increases the expression and secretion of Dickkopf (Dkk) 2, an inhibitor of Wnt/β-linker signaling, which is essential for maintaining muscle and bone function, in the muscles of mice. The research team initially demonstrated that Dkk2 plays a role in muscle and bone alterations in androgen-deficient mice.…”