Naslov
PDGF Regulation of BMP2 Mediated Osteogenesis

Autori
Madunić, Josip ; Shum, Laura ; Vucetic, Milan ; Novak, Sanja ; Kalajzic, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
2020 Annual Meeting of the American Society for Bone and Mineral Research / Civitelli, Roberto - Hoboken (NJ) : John Wiley & Sons, 2020

Skup
Annual Meeting of the American Society for Bone and Mineral Research

Mjesto i datum
Online, 11.09.2020. - 15.09.2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BMP2 ; PDGF ; bone healing ; osteogenesis ; bone defects

Sažetak
Bone healing consists of complex cell interactions regulated by growth factors. Recombinant BMP2 is used in orthopedic treatments to induce bone formation. However, the supraphysiological doses used can cause serious side-effects. PDGF, a mitogenic growth factor highly expressed during bone healing, has also been used to induce bone formation in some clinical applications. Despite the individual abilities of PDGF and BMP2 to induce bone, our previous work showed that PDGF inhibits BMP2-induced osteogenesis in periosteal progenitor cells in vitro. The purpose of the current study was to determine the in vivo role of PDGF on BMP2-mediated osteogenesis. We used critical-sized long bone defects in αSMA9/Col2.3GFP transgenic mice. These mice express the red reporter tdTomato in αSMA+ mesenchymal progenitor cells allowing for analysis of progenitor expansion. Col2.3GFP is expressed in mature osteoblasts and is an indicator of osteogenesis. Critical-sized femoral defects (3 mm) stabilized by external fixation were made in 5-month-old male mice. Growth factors PDGF-BB (2 µg) and BMP2 (0.5 µg or 5 µg), individually or in combination, were applied on the collagen-based material “Infuse” in the defect. αSMA-driven Cre activity was induced by injecting tamoxifen. We assessed defect healing at 2 and 9 weeks using histological analyses. µCT-based morphometry was quantified 9 weeks after defect surgeries. We observed expansion of αSMA+ progenitor cells into the defect following BMP2 treatment and a more pronounced effect with the higher dose. This effect was significantly decreased when the higher dose of BMP2 was combined with PDGF, as quantified by αSMA+ area (p<0.01). At 9 weeks of healing, PDGF and BMP2 individually stimulated osteoblast differentiation, as evidenced by the increase in Col2.3GFP signal corresponding to the areas of new bone formation. However, these effects were inhibited when the growth factors were combined. Although 5 µg BMP2 had biggest impact on bone bridging and bone volume within the defect area, PDGF treatment alone also increased bone volume. Furthermore, μCT data showed that PDGF had inhibited BMP2-induced bone formation, demonstrated by the decrease in bone volume in the defect area (p<0.01). Our in vivo data shows evidence that individual treatments by BMP2 and PDGF-BB induced bone formation, while PDGF exerted negative effects on the osteogenic action of BMP2.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA