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

Abstract

The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insuffi cient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs´ commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specifi c transcriptional regulators. In osteoporosis, the reciprocal balance between the two diff erentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fl uid of control and osteoporotic patients are signifi cantly diff erent. These conclusions should be relevant for the use of MSCs in therapeutic applications.

Potentiation of osteoclastogenesis by adipogenic conversion of bone marrowderivedmesenchymal stem cells

“…As a consequence, osteogenic differentiation from BMSCs is now recognized as an essential part integrated into bone remodelling. Accumulating evidences have also suggested that adipogenesis could play a significant role in bone metabolism (5,8,9,17,24,28,29). For example, since adipocytes and osteoblasts have the same ancestor, osteoblastogenesis and adipogenesis in the bone marrow are regulated in an opposite way, indicating that adipogenic conversion results in a reduction in osteoblast pool (24).…”

The Elevation of Osteoblast Activity in Rat Bone Marrow Mesenchymal Stem Cells in Osteogenic Medium Exposed With Melatonin in Physiological Doses

“…According to Gasser (2003), MSCs for the treatment of osteoporosis requires an osteogenic differentiation agent to be able to differentiate into osteoblasts. Pino et al (2012) reported that in patients with osteoporosis, MSCs tend to differentiate into adipose and not become osteoblasts because of interference on the intrinsic properties and the microenvironment of MSCs. Thus, MSCs therapy for osteoporosis patients brings new hope and melatonin can be considered as a supplement growth factors to obtain the maximum expansion of MSCs and can be used to manage the MSCs to be able to differentiate into osteogenic pathway (Gasser 2003;Zaminyet al 2008;Pino et al 2012).…”

Influence of Donor Age and Passage Number on Angiogenic Activity in Human Adipose-Derived Stem Cell-Conditioned Media

“…Second, underlying diseases in ASC donors were not considered in the present study. Several studies suggest that the number and functional activities of MSCs may be impaired in cells from patients with diseases such as diabetes and osteoporosis [27,51,52]. Third, the angiogenic potential of ASC-CM was evaluated only in the unstimulated condition.…”