The effect of systemically administered PDGF-BB on the rodent skeleton

Abstract

Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks. Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p < 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%). Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone. Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition. We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.

PDGFB-based stem cell gene therapy increases bone strength in the mouse

“…Our findings of increased expression of Csf1 and Tnfsf11, an increased number of TRAP + osteoclasts at the bone surface, and elevated serum CTX-1 levels in PGK-PDGFB-treated mice are entirely consistent with a PDGF-BB-induced increase in bone resorption. Accordingly, inasmuch as the serum PTH was normal in the PGK-PDGFB-treated group, we interpret this finding to be consistent with previous reports on the innate ability of PDGF-BB to stimulate bone resorption (11). Such an increase in bone resorption is indicative of an increase in bone remodeling, which could increase bone quality and improve the mechanical performance of bone.…”

“…We use the term PDGFB to refer the gene that encodes the human platelet-derived growth factor (PDGF) B chain, and the term PDGF-BB to refer the homodimeric protein. PDGF-BB is a major growth factor found in bone matrix (10) and has also been shown to increase bone formation after intravenous administration (11). In addition, there have been considerable successful applications of PDGF-BB-based therapies on various types of maladies, including tendon, periodontal ligament, and bone fracture repairs (12,13).…”

Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet‐derived growth factor‐bb and an injectable beta‐tricalcium phosphate/collagen matrix

“…19 There is clear clinical advantage for ease of use for a single local dose of rhPDGF-BB applied directly to a fracture to accelerate healing that we report, in contrast to a systemic dose administered multiple times as described by Mitlak et al 19 Moreover, Nash et al found rhPDGF-BB combined with a collagen sponge improved fracture repair in a rabbit model. 18 In summary, to the best of our knowledge, this is the first study to report rhPDGF-BB enhanced fracture healing in an osteoporotic animal model that was also geriatric.…”

“…19 Additionally, rhPDGF-BB enhanced bone formation in periodontal defects in dogs. 20 In human patients with advanced periodontal lesions, rhPDGF-BB combined with allograft bone matrix stimulated alveolar bone formation.…”

Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

“…PDGF-BB also increases the number of rat osteoblasts in vivo. 51 In human and murine cells, osteoblast survival is thought be stimulated by PDGF-BB through the phosphorylation of Akt. 52 Therefore, a decrease in osteoclast development and activity may also result from imatinib and nilotinib therapy.…”