Mesenchymal stem cells from development to postnatal joint homeostasis, aging, and disease.

Joint morphogenesis involves signaling pathways and growth factors that recur in the adult life with less redundancy to safeguard joint homeostasis. Loss of such homeostasis due to abnormal signaling networks as in aging could lead to diseases such as osteoarthritis. Stem cells are the cellular counterpart and targets of the morphogenetic signals, and they function to maintain the tissues by ensuring replacement of cells lost to physiological turnover, injury, aging, and disease. Mesenchymal stem cells (MSCs) are key players in regenerative medicine for their ability to differentiate toward multiple lineages such as cartilage and bone, but they age along the host body and senesce when serially passaged in culture. Understanding correlations between aging and its effects on MSCs is of the utmost importance to explain how aging happens and unravel the underlying mechanisms. The investigation of the MSC senescence in culture will help in developing more efficient and standardized cell culture methods for cellular therapies in skeletal regenerative medicine. An important area to explore in biomedical sciences is the role of endogenous stem cell niches in joint homeostasis, remodeling, and disease. It is anticipated that an understanding of the stem cell niches and related remodeling signals will allow the development of pharmacological interventions to support effective joint tissue regeneration, to restore joint homeostasis, and to prevent osteoarthritis.