Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Osteocytes, comprising 90-95% of all cells in hard bone tissue, are increasingly recognised as a critical cell type in bone physiology. We examined the potential role of osteocytes in PJI, with the rationale that their involvement could contribute to the difficulty in detecting and clearing PJI.
S. aureus, the most common pathogen in PJI, was chosen to test for their ability to infect human primary osteocyte-like cells in vitro and human bone samples ex vivo. Bone biopsies were retrieved from patients undergoing revision total hip arthroplasty for either aseptic loosening or PJI. Retrieved bacterial colony number and morphology from cell lysates were determined. Gene expression was measured by microarray and/or qPCR.
Susceptibility of osteocytes to S. aureus was all confirmed in in vitro cell culture, ex vivo organ culture and PJI human bone samples. 24h post-invasion, transcriptome analysis of osteocyte-like cells revealed a strong host immune response. Consistent patterns of host gene expression were observed in both ex vivo infected human bone and in PJI patient bone samples. Internalised bacteria switched to the quasi-dormant small colony variant (SCV) form over 5d and later to a viable but non-culturable (VBNC) form. At a late stage, levels of acute immune response markers were attenuated compared to 5d but remained upregulated.
We have provided evidence for the involvement of human osteocytes in PJI . The multiple events of phenotypic switching of S. aureus suggest that infection of osteocytes may contribute to a chronic disease state. The osteocyte may serve as a reservoir of bacteria for reinfection, perhaps explaining the high prevalence of infections that only become apparent after long periods of time or recur following surgical/medical treatment. Our findings also provide a biological rationale for the recognised need for aggressive bone debridement in the surgical management of PJI.