A complex osteoporotic milieu is associated with arterial stiffening and PDGF-BB-mediated calcification of human smooth muscle cells

Pustlauk, W.; Roch, T.; Dimitriou, I. M.; Blazquez Navarro, A.; Stervbo, U.; Anft, M.; Braun, J.; Wirth, R.; Pourhassan, M.; Buehring, B.; Akguen, D.; Wehler, P.; Skrzypczyk, S.; Gruetz, G.; Rahmann, S.; Seibert, F. S.; Westhoff, T. H.; Babel, N.; Geissler, S.

doi:10.1101/2025.10.25.684499

bioRxiv · 10.1101/2025.10.25.684499

A complex osteoporotic milieu is associated with arterial stiffening and PDGF-BB-mediated calcification of human smooth muscle cells

Pustlauk, W.·Roch, T.·Dimitriou, I. M.·Blazquez Navarro, A.·Stervbo, U.·Anft, M.·Braun, J.·Wirth, R.·Pourhassan, M.·Buehring, B.·Akguen, D.·Wehler, P.·Skrzypczyk, S.·Gruetz, G.·Rahmann, S.·Seibert, F. S.·Westhoff, T. H.·Babel, N.·Geissler, S.

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Abstract

Accumulating evidence links skeletal and vascular aging, yet the pathological cross-talk between osteoporotic bone and vascular calcification remains insufficiently understood. In this retrospective exploratory study, we show that osteoporotic individuals exhibit a distinct systemic milieu characterized by elevated eosinophil, neutrophil, and platelet counts, as well as altered levels of sCD40L, PDGF-BB, osteopontin, and SDF-1. These changes correlate with both bone metabolism and arterial stiffness, indicating a multifactorial bone-vascular interplay. Moreover, osteoporotic sera accelerated calcification of human vascular smooth muscle cells in vitro, with PDGF-BB emerging as a central mediator. Inhibition of PDGF-BB downstream signaling blocked this effect, suggesting a mechanistic role of PDGF-BB in linking the osteoporotic milieu to vascular calcification. Conceptualizing this cross-talk as a complex adaptive system advances our understanding of the disease dynamics between localized bone loss and vascular pathologies. Furthermore, it may guide therapeutic strategies, with PDGF-BB as a potential target, to support healthier aging.

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Pustlauk, W., Roch, T., Dimitriou, I. M., Blazquez Navarro, A., Stervbo, U., Anft, M., Braun, J., Wirth, R., Pourhassan, M., Buehring, B., Akguen, D., Wehler, P., Skrzypczyk, S., Gruetz, G., Rahmann, S., Seibert, F. S., Westhoff, T. H., Babel, N., Geissler, S.. 2025-10-26. A complex osteoporotic milieu is associated with arterial stiffening and PDGF-BB-mediated calcification of human smooth muscle cells. https://doi.org/10.1101/2025.10.25.684499

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