Osteogenesis and aging: lessons from mesenchymal stem cells

Abstract

Aging is a high risk factor for the development of osteoporosis, a multifactorial age-related progressive disease characterized by reduced bone mass and increased risk of fractures. At the cellular level, the mesenchymal stem cell pool in the bone marrow niche shows a biased differentiation into adipogenesis at the cost of osteogenesis. This differentiation shift leads to decreased bone formation, contributing to the etiology of osteoporosis. This review will focus on the most recent/relevant molecular findings driving this functional impairment of mesenchymal stem cells in the aging process.

Keywords: Aging; Differentiation shift; Mesenchymal stem cells; Osteogenesis.

Fig. 1

Osteogenic differentiation of MSCs. The MSC population proliferates actively at the initial stages of osteogenesis. As MSCs commit to osteoblasts their proliferation rate decreases while they start expressing osteogenic markers such as alkaline phosphatase secreted by early osteoblasts (matrix maturation phase) and osteocalcin secreted by late osteoblasts (mineralization phase). At the end of the bone forming phase, they can become BLCs or osteocytes or undergo apoptosis

Fig. 2

Age-related alterations of a number of cell-intrinsic factors can shift MSC differentiation to adipogenesis. Cell-extrinsic factors such as young paracrine factors and ECM, rapamycin, and resveratrol have been proven to restore osteogenic potential of aged MSCs through modulation of these impaired cell-intrinsic factors