Osteocytes contribute to sex-specific differences in osteoarthritic pain

Jones, Ryan, Gilbert, Sophie J., Christofides, Sarah R. and Mason, Deborah J. ORCID: https://orcid.org/0000-0002-8666-6094 2024. Osteocytes contribute to sex-specific differences in osteoarthritic pain. Frontiers in Endocrinology 15 , 1480274. 10.3389/fendo.2024.1480274

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Osteoarthritic (OA) pain affects 18% of females and 9.6% of males aged over 60 worldwide, with 62% of all OA patients being women. The molecular drivers of sex-based differences in OA are unknown. Bone is intricately coupled with the sensory nervous system and one of the only joint tissues known to show changes that correlate with patient pain in OA. There are fundamental sex differences in pain sensation and bone biology which may be intrinsic to OA disease progression, however these differences are vastly under researched. We have utilised three data sets to investigate the hypothesis that potential mediators responsible for sex dependent pain mechanisms displayed in OA are derived from mechanically stimulated osteocytes. Our published dataset of the in vitro human osteocyte mechanosome was independently compared with published data from, sex-based gene expression differences in human long bone, the sex-based gene expression differences during the skeletal maturation of the mouse osteocyte transcriptome and sex specific OA risk factors and effector genes in a large human GWAS. 80 of the 377 sex-specific genes identified in the mouse osteocyte transcriptome were mechanically regulated in osteocytes with enrichment associated with neural crest migration and axon extension, and DISEASES analysis enrichment for the rheumatoid arthritis pathway. 3861 mechanically regulated osteocytic genes displayed sex-specific differences in human long bone with enrichment for genes associated with the synapse, sensory perception of pain, axon guidance, immune responses, distal peripheral sensory neuropathy, sensory neuropathy, and poor wound healing. 32 of 77 effector genes and 1 of 3 female specific OA risk factor genes identified in the human GWAS were differentially expressed in the osteocyte mechanosome and male and female bone. This analysis lends support to the hypothesis that mechanically regulated genes in osteocytes could influence sex specific differences in osteoarthritic pain and highlights pain pathways with approved drugs that could potentially treat elevated pain susceptibility in females with OA.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	Frontiers Media
ISSN:	1664-2392
Date of First Compliant Deposit:	12 November 2024
Date of Acceptance:	16 October 2024
Last Modified:	18 Nov 2024 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/173863

Actions (repository staff only)

Edit Item