Melatonin Promotes Antler Growth by Accelerating MT1-Mediated Mesenchymal Cell Differentiation and Inhibiting VEGF-Induced Degeneration of Chondrocytes

Abstract

The sika deer is one type of seasonal breeding animal, and the growth of its antler is affected by light signals. Melatonin (MLT) is a neuroendocrine hormone synthesized by the pineal gland and plays an important role in controlling the circadian rhythm. Although the MLT/MT1 (melatonin 1A receptor) signal has been identified during antler development, its physiological function remains almost unknown. The role of MLT on antler growth in vivo and in vitro is discussed in this paper. In vivo, MLT implantation was found to significantly increase the weight of antlers. The relative growth rate of antlers showed a remarkable increased trend as well. In vitro, the experiment showed MLT accelerated antler mesenchymal cell differentiation. Further, results revealed that MLT regulated the expression of Collage type II (Col2a) through the MT1 binding mediated transcription of Yes-associated protein 1 (YAP1) in antler mesenchymal cells. In addition, treatment with vascular endothelial growth factor (VEGF) promoted chondrocytes degeneration by downregulating the expression of Col2a and Sox9 (SRY-Box Transcription Factor 9). MLT effectively inhibited VEGF-induced degeneration of antler chondrocytes by inhibiting the Signal transducers and activators of transcription 5/Interleukin-6 (STAT5/IL-6) pathway and activating the AKT/CREB (Cyclin AMP response-element binding protein) pathway dependent on Sox9 expression. Together, our results indicate that MLT plays a vital role in the development of antler cartilage.

Comprehensive transcriptome analysis of sika deer antler using PacBio and Illumina sequencing

“…Meanwhile, Suttie found a strong positive correlation between antler growth rate and circulating IGF-1 concentration, which interacts with testosterone to stimulate intense antler growth 8 . Moreover, previous studies revealed a series of growth factors and signaling pathways involved in the regulation of antler regrowth, including IGF-1 , parathyroid hormone-related peptide, retinoid acid, melatonin, and Wnt signaling pathway 9 , 10 .…”

Special Issue on “Pleiotropic Benefits of Melatonin: From Basic Mechanisms to Disease”

“…Recently, we have demonstrated that melatonin induces a recovery in the functionality of adult hippocampal neurogenesis in aged and neurodegenerative brains of mice with accelerated senescence [ 13 ]. In this respect, Sun and collaborators (2022) also showed that melatonin promotes antler growth in sika deer by accelerating MT1-mediated mesenchymal cell differentiation and inhibiting VEGF-induced degeneration of chondrocytes [ 20 ]. Given the impact of melatonin on cell differentiation processes, an important door is opened towards its potential on cell regeneration mechanisms that should be further investigated.…”