Radovi naših znanstvenika (32)
PDGF inhibits BMP2-induced bone healing npj Regenerative Medicine, https://doi.org/10.1038/s41536-023-00276-5
Autori: Sanja Novak, Josip Madunic, Laura Shum, Milan Vucetic, Xi Wang, Hitoshi Tanigawa, Mallika Ghosh, Archana Sanjay & Ivo Kalajzic
U radu objavljenom u Nature Portfolio časopisu npj Regenerative Medicine (IF:14.4), istražili smo kako delecija receptora PDGFRβ u osteoprogenitorskim stanicama utječe na zacjeljivanje prijeloma kostiju. Koristeći model defekata dugih kostiju, procijenili smo učinke dvaju anaboličkih faktora; PDGF-BB i BMP2, na zacjeljivanje kostiju kod transgeničnih miševa. Naše istraživanje pokazuje da bi modulacija signalnog puta PDGF mogla smanjiti (trenutno korištene) suprafiziološke doze faktora BMP2 i umanjiti neželjene nuspojave uz zadržavanje sposobnosti zacjeljivanja kostiju u kliničkoj terapiji.
Sažetak
Bone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRβ inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models. Targeted deletion of PDGFRβ in αSMA osteoprogenitors, led to increased callus bone mass, resulting in improved biomechanical properties of fractures. In critical size bone defects BMP2 treatment increased proportion of osteoprogenitors, while the combined treatment of PDGF BB with BMP2 decreased progenitor number at the injury site. BMP2 treatment induced significant bone formation and increased number of osteoblasts, while in contrast combined treatment with PDGF BB decreased osteoblast numbers. This is in vivo study showing that PDGF inhibits BMP2-induced osteogenesis, but inhibiting PDGF signaling early in healing process does not improve BMP2-induced bone healing.
Poveznica na članak: https://www.nature.com/articles/s41536-023-00276-5
