Involvement of Adipogenic Potential of Human Bone Marrow Mesenchymal Stem Cells (MSCs) in Osteoporosis

Abstract

Mesenchymal Stem Cells (MSCs) from bone marrow stroma are capable of differentiating into osteoblasts and adipocytes, among other cell phenotypes. In normal bone marrow osteoblastic and adipocytic cell differentiation occur in favor of bone formation, but this relationship appears disrupted in several bone diseases. In osteoporosis increased bone marrow adipocyte production is counterbalanced by diminished production of osteogenic cells. Since osteoblasts and adipocytes originate from a common MSC precursor cell, quantitative and qualitative stem cell defects may underlie the modified number and function of differentiated cells. This review analyzes experimental evidence which describes differences in the osteogenic/adipogenic potentials of human bone marrow MSCs obtained from control and osteoporotic postmenopausal women. The protective effect exerted by locally generated factors, such as estradiol and leptin, on MSCs differentiation was analyzed, because altered bioavailability of these factors may play a part in osteoporosis triggering. Several properties differ among differentiating MSCs from control and osteoporotic donors. Some of these functional differences may be considered to mirror, at the cell level, the detrimental changes displayed in osteoporosis. Osteoporotic MSCs are characterized by increased adipogenic potential, as shown by increased PPARgamma protein content and diminished inactivation of the transcription factor, as compared to control cells. Leptin exerts a direct protective activity against adipogenesis only in control cells. In contrast, leptin activity in MSCs from osteoporotic women appears hampered, suggesting that inadequate leptin activity contributes to excessive lipid accumulation in bone marrow.

In Osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis

“…As pointed out above, MSCs commitment and differentiation into a specifi c phenotype depends on hormonal and local factors (paracrine/autocrine) regulating the expression and/or activity of master diff erentiation genes (Nuttall and Gimble, 2004;Muruganadan et al, 2009) (Figure 1). A reciprocal relationship has been postulated to exist between the two differentiation pathways whose alteration would facilitate adipose accretion in the bone marrow, at the expense of osteoblast formation, thus decreasing bone mass (Reviewed in Rosen et, al 2009;Rodríguez et al. 2008;Rosen and Bouxtein, 2006).…”

Flavonoids of Herba Epimedii stimulate osteogenic differentiation and suppress adipogenic differentiation of primary mesenchymal stem cells via estrogen receptor pathway

“…In normal bone marrow, osteoblastic and adipocytic differentiation of MSCs occurs in favor of bone formation, which was disrupted in several bone diseases. In the process of osteoporosis, increased bone marrow adipocyte production is counterbalanced by diminished production of osteogenic cells, and the deficiency in osteogenesis from MSCs resulted in various bone diseases (Rodriguez et al, 2008). Accumulating evidence suggests that Herba Epimedii [Epimedii folium (Berberidaceae)] has the potential benefits against osteoporosis, which was traditionally widely used for preventing and treating osteoporosis in Asia.…”

The Effect of Estrogen on Bone Marrow-Derived Rat Mesenchymal Stem Cell Maintenance: Inhibiting Apoptosis Through the Expression of Bcl-xL and Bcl-2

“…Estrogen has been shown to have an important role on adipocyte metabolism [32] and our results provided support that this effect might also be at the level of differentiation. It has been reported that MSCs from osteoporotic post-menopausal women showed an increase in PPARγ expression and thus an increase in adipocytes [33]. In addition, serum from post menopausal in comparison to serum from pre-menopausal women, were able to induce adipogenic differentiation in a human bone progenitor cell clone (hOP 7) derived from bone marrow [34].…”