20.500.12556/DiRROS-29193 Bone mechano-response is driven by locomotion transitions during vertebrate evolution The skeleton supports the muscles in keeping the body upright against gravity while enduring thousands of daily loads. In this study, we investigated non-collagenous bone matrix proteins using osteoblast cell cultures and phylogenetic analyses to identify the molecular mechanisms involved in mechanical loading. The results indicate that several non-collagenous proteins may significantly regulate the bone’s response to mechanical stress. Furthermore, we hypothesize that the bone mechano-response is an evolutionary-driven process. The selection analysis indicates that two of the major evolutionary transitions in vertebrate locomotion shaped the roles of non-collagenous proteins in the bone matrix: the water-to-land transition, which increased mechanical stress on the limbs, and the evolution to bipedalism in humans, which altered the distribution of stress on the lower and upper limbs. Fetuin A, positively selected in both evolutionary transitions, showed the most significant expression change during the mechanical stimulation experiments. osteoblast cell culture mechanical loading non‑collagenous bone matrix proteins Fetuin A true false true Angleški jezik Ni določen Neznano 2026-04-23 14:58:08 2026-04-23 14:58:09 2026-04-24 04:05:32 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 10. 4. 2026; str. 1-9 [article no.] 31 Vol. 9 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61 2399-3642 10.1038/s42003-025-09292-1 274774787 RAZ_Shimochi_Saeka_2026.pdf RAZ_Shimochi_Saeka_2026.pdf 1 924CAD853E9946258043EEC752850796 5d81bc318db59212609b7d5e4f140f534adbc329f95b7503187f0b1135b94325 30903511-3f14-11f1-b867-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43650 https://www.nature.com/articles/s42003-025-09292-1 1 16c1d9fc-3f14-11f1-b867-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43649 Univerzitetni klinični center Ljubljana 0 0 0