No abstract

The aim of the present study was to elucidate the role of osteoblasts in bisphosphonates-related osteonecrosis of the jaw (BRONJ). The specific objective was to evaluate the effect on osteoblasts of two nitrogen-containing BPs (zoledronate and alendronate) and one non-nitrogen-containing BP (clodronate) by analyzing modulations in their expression of genes essential for osteoblast physiology. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of zoledronate, alendronate, and clodronate at doses of 10-5, 10-7, or 10-9 M on the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-β1, VEGF, TGF-βR1, TGF-βR2, and TGF-βR3 by primary human osteoblasts (HOBs) and MG-63 osteosarcoma cells. Expression of these markers was found to be dose-dependent, with no substantive differences between these cell lines. In general, results demonstrated a significant increase in TFG-β1, TGF-βR1, TGF-βR2, TGF-βR3, and VEGF expressions and a significant reduction in RUNX-2, Col-1, OSX, OSC, BMP-2, BMP-7, ALP, and RANKL expressions, while OPG expression varied according to the dose and cell line. The results of this in vitro study of HOBS and MG-63 cell lines indicate that low BP doses can significantly affect the expression of genes essential for osteoblast growth and differentiation and of genes involved in regulating osteoblast-osteoclast interaction, possibly by increasing TGF-β1 production. These findings suggest that osteoblasts may play an important role in BRONJ development, without ruling out other factors.

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

Platelet-rich growth factor (PRGF) is a natural source of growth factors (GF), while hyaluronic acid (HA) is a biopolymer present in the extracellular matrix of skin, cartilage, bone, and brain, among other tissues. Both are involved in the pathophysiological mechanisms underlying wound healing. The objective of this study was to evaluate the clinical efficacy (as measured by ulcer area) and safety (as measured by signs of infection) of PRGF and PRGF plus HA in the treatment of pressure ulcers (PUs). Patients (N = 100) with 124 Stage II-III PUs were randomized to a control group (n = 25 PUs) for standard care or to case groups for treatment with one (n = 34 PUs) or two (n = 25 PUs) doses of PRGF from their own peripheral blood, or two doses of PRGF plus HA (n = 40 PUs). All ulcers were followed up every 3 days for a 36-day period. At 36 days, a significant reduction in ulcer area (p ≤ .001) was observed in all treatment groups, with a mean reduction of more than 48.0% versus baseline. The greatest mean reduction (80.4% vs. baseline) was obtained with the PRGF plus HA regimen. Complete wound healing was observed in 32.0% of PUs treated with two doses of PRGF (p ≤ .002) and in 37.5% of those treated with two doses of PRGF plus HA (p ≤ .004). There were no signs of infection in any PUs during the 36-day follow-up period. The degree of wound healing was inversely correlated with the consumption of drugs such as statins and with the peripheral blood platelet levels of patients at baseline.