Bothrops moojeni Venom and Its Components Strongly Affect Osteoclasts' Maturation and Protein Patterns

Area of Science:

• Biochemistry
• Immunology
• Toxicology

Background:

• Osteoclasts (OCs) are crucial for bone remodeling, calcium homeostasis, and tissue repair.
• Dysfunctional osteoclasts are implicated in various inflammatory bone diseases.
• The venom of Bothrops moojeni, a Brazilian pit viper, possesses a complex composition with unexplored biological activities.

Purpose of the Study:

• To investigate the in vitro effects of Bothrops moojeni venom and its molecular mass fractions on human osteoclast differentiation.
• To assess the venom's impact on osteoclast morphology and function, specifically F-actin ring integrity.
• To explore the molecular mechanisms underlying venom-induced osteoclast modulation using proteomic analysis.

Main Methods:

• Human peripheral blood mononuclear cells (PBMCs) were differentiated into osteoclasts in vitro.
• Bothrops moojeni venom and its High Molecular Mass (HMM) and Low Molecular Mass (LMM) fractions were applied at varying concentrations.
• Osteoclast differentiation was assessed by TRAP staining, F-actin ring integrity was visualized by phalloidin staining, and secreted proteins were analyzed by LC-MS/IT-Tof mass spectrometry.

Main Results:

• Bothrops moojeni venom significantly reduced the number of TRAP+ osteoclasts at a concentration of 5 µg/mL.
• The venom disrupted the F-actin ring structure in osteoclasts, indicating impaired bone resorption capacity.
• HMM fraction inhibited TRAP+ osteoclasts at 5 µg/mL, while LMM fraction showed inhibition at 1 µg/mL, with proteomic analysis revealing potential molecular pathways involved.

Conclusions:

• Bothrops moojeni venom and its fractions exhibit potent inhibitory effects on osteoclast differentiation and function in vitro.
• The venom induces morphological changes in osteoclasts, compromising their bone-resorbing activity.
• These findings highlight the potential of Bothrops moojeni venom components as novel therapeutic agents for managing inflammatory bone disorders.