Abnormal changes in the quantity and function of osteoblasts cultured in�vitro in patients with myelodysplastic syndrome

Abstract

Changes in bone marrow niches can lead to the occurrence of myelodysplastic syndrome (MDS). As an important part of the bone marrow niche, osteoblasts serve a key role in the progression of MDS. The present study investigated the quantity and function of osteoblasts and, through in vitro assays, detected changes in signaling pathways and the association with progression in MDS patients. The ratios of osteoprogenitors (CD34+OCN+) and OCN+CD34−Lin− osteoblasts in MDS patients were significantly less than those of normal controls. The results of this study demonstrated that the quantity and activity of osteoblasts in MDS patients were lower than those in normal controls. Furthermore the activity of osteoblasts in patients correlated with the severity of MDS. The quantity of osteoblasts cultured in vitro from high-risk and very high-risk MDS patients (WHO Classification-Based Prognostic Scoring System score 3–6) was decreased. The levels of T-cell immunoglobulin and mucin domain-containing 3 (TIM3) and Jagged 1 were also increased in the osteoblasts in vitro. These results indicated that osteoblasts are abnormally altered in MDS patients, and that there are associations between abnormal changes of osteoblasts and the severity of MDS.

In vivo bone regeneration assessment of offset and gradient melt electrowritten (MEW) PCL scaffolds

“…This may be due to the gradient porous structure allowing more tissue ingrowth and blood vessels that result in a cooperative angiogenesis mechanism of CD34 and VEGF along with Ocn at week 8 and vWF at week 4 that increased the speed of new bone regeneration through the nutrient and oxygen flow improvement [70] in comparison to smaller pore sizes. This is in accordance with the studies of Gao and Bolander who demonstrated that the Ocn + CD34+ cell population displayed more mature osteoblasts and mineralized matrix tissue in vitro [71,72] which is due to the paracrine effect of CD34 + cells that causes the secretion of VEGF and their synergistic angiogenesis/ osteogenesis signals on bone regeneration [73].…”