Human parvovirus B19 VP1u protein drives osteoclastogenesis via p38 MAPK pathway in macrophages

Maintaining bone homeostasis relies on a delicate balance between osteoblast and osteoclast activity. Disruptions, often driven by chronic inflammation, can lead to enhanced osteoclast activity and subsequent bone loss. Human parvovirus B19 (B19V) DNA and antigens are frequently found in synovial tissue, suggesting a role in bone destruction, yet the precise mechanisms linking B19V infection to this pathology remain unclear. Understanding how viral components like the VP1 unique region (VP1u) influence osteoclastogenesis could reveal novel therapeutic targets for B19V-associated bone erosion.

Researchers investigated the B19V VP1u protein's influence on osteoclast differentiation using RAW264.7 macrophages. Cells were cultured with or without B19V-VP1u (in a dose-dependent manner) and/or receptor activator of NF-κB ligand (RANKL) for up to 7 days. Osteoclastogenesis was assessed via tartrate-resistant acid phosphatase (TRAP) staining, bone resorption assays, and western blotting. The involvement of specific signaling pathways was explored using an anti-TNF-α antibody and inhibitors targeting MAPK, ERK, JNK, and NF-κB signaling.

B19V-VP1u alone induced osteoclastogenesis in a dose- and time-dependent manner. In the presence of RANKL, B19V-VP1u further increased osteoclast size and number. The study found that B19V-VP1u significantly increased pit resorption, a key indicator of bone degradation. Furthermore, it elevated the expression of crucial osteoclast markers including NFAT2 (also known as NFATc1), cathepsin K, c-FOS, MMP9, and dendritic cell-specific transmembrane protein (DC-STAMP). > Blockade of p38 MAPK nearly abolished B19V-VP1u-induced osteoclastogenesis, indicating a direct, p38-dependent mechanism. Conversely, inhibition of ERK, JNK, NF-κB, or TNF-α did not alter the effects of VP1u, suggesting these pathways are not primary mediators of VP1u's direct osteoclastogenic action.