An international study with the participation of La Salle-URL, through researcher Miho Nakamura, reveals how evolution and locomotion patterns, such as bipedalism, have shaped skeletal structures through proteins in the bone matrix. The study has recently been published in Communications Biology, a prestigious scientific journal from the Nature group, and has been jointly coordinated by researchers from La Salle-URL, the Universitat Autònoma de Barcelona (UAB) and the University of Turku (Finland).
The bones of vertebrates constantly detect and respond to mechanical forces, a phenomenon known as mechanoadaptation. The new study shows that this capacity has been shaped not only by biomechanics, but also by millions of years of evolutionary pressure linked to locomotion. Species with different locomotor patterns display distinct evolutionary signatures in the genes and proteins associated with load and impact detection and with skeletal remodeling.
“These results indicate that the evolution of locomotion has played a fundamental role in shaping the molecular machinery of bone mechanoadaptation,” says Professor Pere Puigbò, from the Serra Húnter Programme (Department of Animal Science and Food Science, UAB). Two of these decisive moments were the transition of vertebrates from water to land, which increased stress on the limbs, and the emergence of bipedalism in humans, which redistributed mechanical stress between the arms and legs.
The study identifies several non-collagenous proteins of the bone matrix that may act as key regulators of mechanotransduction, many of which have received little attention in previous research. These findings provide new insights into how bone cells detect and respond to external forces and how these mechanisms have been modulated throughout vertebrate evolution. “From a cellular biology perspective, our work highlights important but undervalued proteins that could be central to bone remodeling,” adds La Salle-URL researcher Miho Nakamura.
The findings are relevant for understanding bone regeneration, bone fragility, and osteoporosis, and may help guide the development of biomaterials inspired by the natural adaptation of the skeleton. The study highlights several non-collagenous proteins, including fetuin-A, which regulates mineral deposition and prevents abnormal calcification. Fetuin-A plays a crucial role in maintaining healthy bones and may influence the risk of osteoporosis by balancing bone formation and resorption.
Building on these discoveries, the Phylobone research group—coordinated by both researchers and dedicated to studying bone regeneration from an evolutionary biology perspective—is investigating how these proteins drive skeletal adaptation and bone remodeling. The study, conducted using bone cell cultures and phylogenetic analyses, was funded by the Sigrid Jusélius Foundation (Finland) and the Japan Society for the Promotion of Science (Japan).
Scientific article reference
Shimochi S, Brunet C, Fontcuberta-Rigo M, Hrovat K, Puigbò P, Nakamura M. «Bone mechano-response is driven by locomotion transitions during vertebrate evolution». Communications Biology (2025). https://doi.org/10.1038/s42003-025-09292-1
