Probing the response of human osteoblasts following exposure to sympathetic neuron-like PC-12 cells in a 3D coculture model.

Understanding the capacity of the sympathetic nervous system (SNS) to regulate bone homeostasis has implications for a number of metabolic diseases and may help establish connections between certain neurological conditions and bone quality. The goal of the present work was to gain a deeper understanding of the influence of the SNS on the phenotype of osteoblasts, a major cell type in bone. An in vitro coculture model with human osteoblasts and sympathetic-like, neuroendocrine pheochromocytoma-12 (PC-12) cells encapsulated within separate 3D poly(ethylene glycol) diacrylate (PEGDA) hydrogels was utilized to assess markers involved with bone ECM formation and osteoclast formation. In terms of bone ECM proteins, only osteopontin (OPN) was significantly increased in osteoblasts exposed to PC-12 cells relative to osteoblast mono-culture controls. In contrast, all bone resorption markers investigated (IL-6, TNF, IL-1β, VEGF-A) were enhanced at the gene level and the ratio of osteoprotegerin (OPG) to RANKL was significantly decreased in osteoblasts exposed to PC-12 cells. Cumulatively, these data indicate that the SNS may substantially influence bone resorption. Because of the context-dependent nature of the SNS, future studies will characterize the secretion profile of neurotransmitters and neuropeptides from the PC-12 cells in our model. Additionally, various SNS modulating pharmacologic agents will be examined for their capacity to reduce expression of bone resorption/inflammatory markers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 984-990, 2017.