Chlorogenic Acid Alleviates Thiram-Induced Tibial Dyschondroplasia by Modulating Caspases, BECN1 Expression and ECM Degradation

Int J Mol Sci. 2019 Jun 28;20(13):3160. doi: 10.3390/ijms20133160.

Abstract

Chlorogenic acid (CGA) is a widely applied traditional Chinese medicine ingredient which can be used for the treatment of osteoporosis. In this experiment, we investigated the potential therapeutic effect of chlorogenic acid on thiram-induced tibial dyschondroplasia (TD) and explored the underlying mechanisms that have been rarely mentioned by others yet. Performance indicator analysis and tibial parameter analysis showed that CGA exhibited a definite positive effect on thiram-induced TD chickens. In order to further explore the mechanisms underlying the positive actions of CGA, apoptotic, autophagic genes and MMPs involved in matrix mineralization of growth plate were evaluated in this study. The results showed that CGA decreased the expression of pro-apoptotic genes caspases-3 and caspases-9, leading to the reduction of apoptotic cells accumulated in growth plate. In addition, CGA also increased the level of BECN1, an important gene involved in autophagy, which benefits the survival of abnormal cells. Furthermore, CGA also increased the expression of MMP-9, MMP-10, and MMP-13, which can directly affect the ossification of bones. Altogether, these results demonstrate that CGA possesses a positive therapeutic effect on thiram-induced TD via modulating the expression of caspases and BECN1 and regulating the degradation of ECM (extracellular matrix).

Keywords: apoptosis; autophagy; chlorogenic acid; growth plate; matrix mineralization; tibial dyschondroplasia.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Beclin-1 / genetics
  • Beclin-1 / metabolism*
  • Caspases / genetics
  • Caspases / metabolism
  • Chickens
  • Chlorogenic Acid / pharmacology
  • Chlorogenic Acid / therapeutic use*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Osteochondrodysplasias / drug therapy*
  • Osteochondrodysplasias / etiology
  • Thiram / toxicity
  • Tibia / drug effects
  • Tibia / metabolism
  • Tibia / pathology

Substances

  • Beclin-1
  • Thiram
  • Chlorogenic Acid
  • Caspases
  • Matrix Metalloproteinases