Transcriptomic Dissection of Bothrops moojeni Venom Reveals Fraction-Specific Modulation of Host Cellular Pathways

Snake venom is a remarkably complex cocktail of bioactive molecules capable of hijacking diverse host physiological processes, yet how individual venom components drive these cellular responses remains a bit of a black box. To map these dynamics, we ran a comparative transcriptomic analysis on human osteoclastogenic cultures, exposing them continuously to crude Bothrops moojeni venom and its high (HMM) and low (LMM) molecular mass fractions throughout differentiation. This allowed us to capture the cumulative transcriptional shifts that unfold across the entire lifecycle of osteoclast development. The crude venom triggered a sweeping response, deeply impacting neuroimmune, extracellular matrix remodeling, inflammatory, and apoptotic pathways—reflecting a massive reshuffling of cellular regulatory networks. When we looked at the fractions, clear dividing lines emerged. The HMM fraction, packed with metalloproteinases and serine proteases, mostly drove pathways tied to cytoskeletal remodeling, intracellular trafficking, and osteoclast-associated signaling. In contrast, the LMM fraction—home to phospholipases A2, disintegrins, and small peptides—steered a much more targeted course, influencing immune regulation, proliferative signaling, and metabolic homeostasis while noticeably turning down catalytic and binding functions. Interestingly, all venom-treated groups shared a drop-off in ATP-dependent and ligand-binding categories, pointing to a common disruption in core metabolic and signaling processes. Taken together, these findings offer a clearer mechanistic look at how different B. moojeni venom components target bone remodeling pathways, highlighting the power of transcriptomics for untangling complex venom–host interactions.