Osteogenic Differentiation in Healthy and Pathological Conditions

Abstract

This review focuses on the osteogenic differentiation of mesenchymal stem cells (MSC), bone formation and turn-over in good and ill skeletal fates. The interacting molecular pathways which control bone remodeling in physiological conditions during a lifelong process are described. Then, alterations of the molecular pathways regulating osteogenesis are addressed. In the aging process, as well as in glucocorticoid-induced osteoporosis, bone loss is caused not only by an unbalanced bone resorption activity, but also by an impairment of MSCs' commitment towards the osteogenic lineage, in favour of adipogenesis. Mutations affecting the expression of key genes involved in the control of bone development occur in several heritable bone disorders. A few examples are described in order to illustrate the pathological consequences of perturbation in different steps of osteogenic commitment, osteoblast maturation, and matrix mineralization, respectively. The involvement of abnormal MSC differentiation in cancer is then discussed. Finally, a brief overview of clinical applications of MSCs in bone regeneration and repair is presented.

Keywords: Pigment Epithelium Derived Factor (PEDF); Runt-related transcription factor 2 (RUNX2); Wingless-Type MMTV Integration Site Family (WNT); bone; mesenchymal stem cells; microRNAs; osteoblasts; osteopenia; remodeling.

Figure 1

Schematic representation of cell types and major regulators of the molecular pathways involved in osteoblastogenesis and bone formation.

Figure 2

Defects in bone mineralization due to the lack of PEDF. (A) Iliac bone section of a patient affected by OI type VI. A large amount of unmineralized osteoid (in red) and resorption lacunae are visible. (B) Bone section under polarized light. Black arrows point to the so called “fish-scale” pattern (magnification 200×) (Reproduced from J. Bone Miner. Res. 2012, 50, 343–349, with permission of the American Society for Bone and Mineral Research). The insert in (B) shows an enlargement of fish scale (2000×).