Abstract

BackgroundThe aim of this study was the investigation of the osteogenic potential of human osteoblasts of advanced donor age in 2D and 3D culture.MethodsOsteoblasts were induced to osteogenic differentiation and cultivated, using the same polystyrene material in 2D and 3D culture for 2 weeks. Samples were taken to evaluate alkaline phosphatase (ALP) activity, mineralization and gene expression.ResultsOsteoprotegerin (OPG) levels were significantly increased (8.2-fold) on day 7 in 3D compared to day 0 (p < 0.0001) and 11.6-fold higher in 3D than in 2D (p < 0.0001). Both culture systems showed reduced osteocalcin (OC) levels (2D 85% and 3D 50% of basic value). Collagen type 1 (Col1) expression was elevated in 3D on day 7 (1.4-fold; p = 0.009). Osteopontin (OP) expression showed 6.5-fold higher levels on day 7 (p = 0.002) in 3D than in 2D. Mineralization was significantly higher in 3D on day 14 (p = 0.0002).ConclusionAdvanced donor age human primary osteoblasts reveal significantly higher gene expression levels of OPG, Col1 and OP in 3D than in monolayer. Therefore, it seems that a relatively high potential of bone formation in a natural 3D arrangement is presumably still present in osteoblasts of elderly people.Trial registration5217/11 on the 22nd of Dec. 2011.

Highlights

  • Trauma of the elderly is a rising issue in trauma and orthopaedic surgery

  • A further cellular mechanism for bone loss is an impairment of the osteogenic potential because of decreased Mesenchymal stem cell (MSC) leading to reduced expression of osteoblastic markers [10, 11]

  • Several growth factors that enhance osteoblast activity and bone formation include insulin-like growth factors (IGFs) [15, 16], bone morphogenetic proteins (BMPs) [17] and prostaglandins [18]

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Summary

Introduction

Trauma of the elderly is a rising issue in trauma and orthopaedic surgery. Fracture healing itself is a complex physiologic process in which numerous cytokines, angiogenic factors, proteases and morphogens with significant roles are involved [1, 2]. Age-related bone loss is characterized by reduced bone formation due to decreased number of osteoblasts and lowered activity. A further cellular mechanism for bone loss is an impairment of the osteogenic potential because of decreased MSCs leading to reduced expression of osteoblastic markers [10, 11]. Age-related osteoblast dysfunction is associated with impaired proliferation, a decline in functional lifespan and a decrease in differentiation, function and activity [10]. These age-related changes are caused by extrinsic mechanisms mediated by hormones and growth factors and intrinsic mechanisms caused by osteoblastic cell senescence [12]. The aim of this study was the investigation of the osteogenic potential of human osteoblasts of advanced donor age in 2D and 3D culture

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