Molecular Basis of Bone Aging

Abstract

A decline in bone mass leading to an increased fracture risk is a common feature of age-related bone changes. The mechanisms underlying bone senescence are very complex and implicate systemic and local factors and are the result of the combination of several changes occurring at the cellular, tissue and structural levels; they include alterations of bone cell differentiation and activity, oxidative stress, genetic damage and the altered responses of bone cells to various biological signals and to mechanical loading. The molecular mechanisms responsible for these changes remain greatly unclear and many data derived from in vitro or animal studies appear to be conflicting and heterogeneous, probably due to the different experimental approaches; nevertheless, understanding the main physio-pathological processes that cause bone senescence is essential for the development of new potential therapeutic options for treating age-related bone loss. This article reviews the current knowledge concerning the molecular mechanisms underlying the pathogenesis of age-related bone changes.

Osteoprotective Roles of Green Tea Catechins

“…Both runt-related transcription factor 2 (Runx2) [ 10 ] and Osterix (Osx) [ 11 ], also known as SP7 in human [ 12 ], control osteoblastic differentiation of MSCs [ 9 ]. Osteogenic differentiation can be enhanced by bone morphogenetic proteins (BMPs), a member of the transforming tumor growth factor (TGF) superfamily, through increasing Runx2 expression, which in turn raises Osx/SP7 expression [ 13 ]. Conversely, Wnt signaling inhibits adipogenesis by stimulating Runx2 and inhibiting CCAAT-enhancer binding protein α (C/EBP α) [ 13 ].…”

“…Osteogenic differentiation can be enhanced by bone morphogenetic proteins (BMPs), a member of the transforming tumor growth factor (TGF) superfamily, through increasing Runx2 expression, which in turn raises Osx/SP7 expression [ 13 ]. Conversely, Wnt signaling inhibits adipogenesis by stimulating Runx2 and inhibiting CCAAT-enhancer binding protein α (C/EBP α) [ 13 ]. Excessive oxidative stress may cause increased reactive oxygen species (ROS), increased phosphorylation of p53 and p66, and decreased expression of β-catenin, leading to apoptosis of osteoblasts [ 14 , 15 , 16 , 17 ].…”

“…Inflammatory cytokines, including IL-1, TNFα, IL-6, and IL-17, enhance osteoclastogenesis and prohibit the differentiation and function of osteoblasts. Moreover, interferon (IFN)-γ, IL-10, IL-4, and IL-12 prohibit osteoclastogenesis, while IL-4 enhances osteoblast migration and proliferation and inhibits osteoblast differentiation [ 13 ].…”

Vitamin D, Bone Metabolism, and Fracture Risk in Polycystic Ovary Syndrome

“…It has been observed that vitamin D supplementation in PCOS women may improve the steroidogenesis and enzymatic antioxidant activity in the human GC [ 94 ] and it may attenuate the actions of AGEs [ 95 , 96 ]. AGEs play a role in age-related bone loss [ 97 , 98 ]. AGEs provoke bone cell impairment and alter bone biomechanical properties.…”

Is a Healthy Diet Also Suitable for the Prevention of Fragility Fractures?

“…Moreover, osteoblast and osteoclast recruitment and activity can be affected by different cytokines. The inflammatory cytokines, for example, tumor necrosis factor α and the interleukins 1, 6 and 17, promote the generation of osteoclasts and their activity, while at the same time inhibit osteoblast differentiation and function [47]. These processes may also contribute to the loss of muscle mass and the development of sarcopenia [2,3].…”