Lipoteichoic Acid Rescued Age-Related Bone Loss by Enhancing Neuroendocrine and Growth Hormone Secretion Through TLR2/COX2/PGE2 Signalling Pathway

J Cell Mol Med. 2024 Dec;28(23):e70247. doi: 10.1111/jcmm.70247.

Abstract

The phenomenon of brain-bone crosstalk pertains to the intricate interaction and communication pathways between the central nervous system and the skeletal system. Disruption in brain-bone crosstalk, particularly in disorders such as osteoporosis, can result in skeletal irregularities. Consequently, investigating and comprehending this communication network holds paramount importance in the realm of bone disease prevention and management. In this study, we found that Staphylococcus aureus lipoteichoic acid promoted the conversion of arachidonic acid to PGE2 by interacting with TLR2 receptors acting on the surface of microglial cells in the pituitary gland, leading to the upregulation of COX-2 expression. Subsequently, PGE2 bound to the EP4 receptor of growth hormone-secreting cells and activated the intracellular CREB signalling pathway, promoting GH secretion and ameliorating age-related bone loss.

Keywords: PGE2; bone loss; brain–bone; growth hormone; lipoteichoic acid.

MeSH terms

  • Aging / metabolism
  • Animals
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclooxygenase 2* / metabolism
  • Dinoprostone* / metabolism
  • Growth Hormone* / metabolism
  • Lipopolysaccharides*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / metabolism
  • Neurosecretory Systems / metabolism
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Signal Transduction* / drug effects
  • Staphylococcus aureus
  • Teichoic Acids* / pharmacology
  • Toll-Like Receptor 2* / metabolism

Substances

  • Lipopolysaccharides
  • Teichoic Acids
  • Toll-Like Receptor 2
  • lipoteichoic acid
  • Dinoprostone
  • Cyclooxygenase 2
  • Growth Hormone
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclic AMP Response Element-Binding Protein