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Abstract
It is assumed that the activity of osteoblasts and osteoclasts is decreased in bone tissue of aged individuals. However, detailed investigation of the molecular signature of human bone from young compared to aged individuals confirming this assumption is lacking. In this study, quantitative expression analysis of genes related to osteogenesis and osteoclastogenesis of human cancellous bone derived from the distal radius of young and aged individuals was performed. Furthermore, we additionally performed immunohistochemical stainings. The young group included 24 individuals with an average age of 23.2 years, which was compared to cancellous bone derived from 11 body donators with an average age of 81.0 years. In cancellous bone of young individuals, the osteogenesis‐related genes RUNX‐2,OSTERIX,OSTEOPONTIN and OSTEOCALCIN were significantly up‐regulated compared to aged individuals. In addition, RANKL and NFATc1, both markers for osteoclastogenesis, were significantly induced in cancellous bone of young individuals, as well as the WNT gene family member WNT5a and the matrix metalloproteinases MMP‐9. However, quantitative RT‐PCR analysis of BMP‐2,ALP,FGF‐2,CYCLIN‐D1,MMP‐13,RANK,OSTEOPROTEGERIN and TGFb1 revealed no significant difference. Furthermore, Tartrate‐resistant acid phosphatase (TRAP) staining was performed which indicated an increased osteoclast activity in cancellous bone of young individuals. In addition, pentachrome stainings revealed significantly less mineralized bone matrix, more osteoid and an increased bone density in young individuals. In summary, markers related to osteogenesis as well as osteoclastogenesis were significantly decreased in the aged individuals. Thus, the present data extends the knowledge about reduced bone regeneration and healing capacity observed in aged individuals.
Highlights
Bone remodelling is a dynamic process which starts at the early embryonic stage and sustains throughout life-time and is tightly regulated by bone-building osteoblasts (OB) and bone resorbing osteoclasts (OC)
We performed quantitative RT-PCR analyses to obtain expression profiles of osteogenesis and osteoclastogenesis-related genes of human cancellous bone from young and aged individuals
As detailed information about the molecular mechanisms leading to altered bone homoeostasis in aged human bone is rare, we analysed the expression of several osteogenesis- and osteoclastogenesis-related markers by quantitative RT-PCR, histology and immunohistochemistry in human cancellous bone of young and aged donors
Summary
Bone remodelling is a dynamic process which starts at the early embryonic stage and sustains throughout life-time and is tightly regulated by bone-building osteoblasts (OB) and bone resorbing osteoclasts (OC). Bone homoeostasis seems to be affected by progressive deprivation of cell function and proliferation [1, 2]. Regulation of bone remodelling could be impaired resulting in decreased bone density and fragile bone structure. Previous studies indicated that aged individuals have a 10-fold increased fracture risk compared to young individuals [3, 4]. Demographic data indicated that 79% of the total German population is younger than 65 years (Web Reference 1). The German Federal Health Reporting in 2014 stated 360,000 bone fractures (Web Reference 2). Changing of composition of the society0s age indicates that the risk of fractures leading to impaired bone healing steadily increases, which makes a better understanding of bone ageing and homoeostasis indispensable
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