Introduction. Experimental possibilities during actual spaceflight are limited, making ground-based models, such as dry immersion (DI) and head-down bed rest (HDBR) tests, highly relevant. Changes in bone tissue are induced by alterations in a complex set of environmental factors at the proteomic level, compensating for changes caused by reduced gravity and decreased motor activity. However, upon continued exposure, other regulatory circuits are activated.

Objective. Comparative assessment of proteomic regulation of bone tissue status in 21-day HDBR (tilted at 6°) and 21-day DI tests.

Materials and methods. Using mass spectrometry methods, plasma samples from 8 healthy male volunteer subjects (mean age 20–44 years) under the conditions of 21-day HDBR and 10 subjects (mean age 23–34 years) under 21-day DI were studied. The Perseus software was used for statistical analysis and identification of molecular functions and biological processes involving the proteins. The correspondence of major biological processes, according to gene ontologies specified in the GO database, and identified proteins was established using the knowledge base of the ANDSystem and STRING.

Results. Nine proteins with significantly altered levels on Day 21 of HDBR (p < 0.05) and eight proteins with significantly altered levels on Day 21 of DI (p < 0.05) were identified. These proteins are associated with biological processes occurring in bone tissue. Some of the identified proteins form stable protein–protein interaction (PPI) networks, indicating potential co-expression. Two common proteins — haptoglobin (Hp) and glutathione peroxidase (GPx) — were identified on Day 21 of both DI and HDBR.

Conclusions. The findings offer an insight into the proteomic mechanisms regulating biological processes in bone tissue of healthy individuals under the influence of 21-day HDBR and 21-day DI. Annotations for each protein involved in bone tissue biological processes during 21-day HDBR (tilted at 6°) and 21-day DI are provided. These results are of great importance for aerospace and clinical medicine.