Adipose-derived stem cells may help treat osteoporosis
MedWire News: Human adipose-derived stem cells (hASCs) may be a valuable tool in osteoporosis therapy, Korean researchers report.
Daewon Jeong (Yeungnam University College of Medicine, Daegu) and colleagues found that hASCs secreted cytokines, growth factors, and proteins - collectively known as paracrine factors. These factors reduced estrogen deficiency-induced bone loss in ovariectomized (OVX) mice by simultaneous stimulation of osteoblast-mediated bone formation, and osteoclast-mediated bone resorption.
"Systemic transplantation of ASCs is emerging as a novel therapeutic option for functional recovery of diverse damaged tissues," explain Jeong et al in the Journal of Cellular and Molecular Medicine.
In the present study, the researchers investigated the effects of hASC systemic transplantation on bone repair using an OVX-induced osteoporotic mouse model.
They found that hASCs secreted various paracrine factors required for bone function and remodeling, including hepatocyte growth factor, macrophage colony-stimulating factor (M-CSF), bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, receptor activator of nuclear factor kappa-B ligand, and tumor necrosis factor-α.
Compared with sham-operated and non-transplanted OVX mice, systemic transplantation of hASCs into OVX mice resulted in increased numbers of osteoblasts and osteoclasts on bone surfaces.
Furthermore, hASCs prevented OVX-induced bone loss in mice, as demonstrated by increased bone volume fraction, trabecular number, and bone mineral density compared with non-transplanted OVX mice.
To understand the molecular mechanisms responsible for the in vivo results, Jeong and team investigated whether conditioned culture medium from hASCs could affect the physiological properties of osteoblasts and osteoclasts.
In vitro findings revealed that hASCs stimulate proliferation and differentiation of osteoblasts via Smad/extracellular signal-related kinase (ERK)/jun NH2-terminal kinase (JNK) activation, as well as survival and differentiation of osteoclasts via ERK/JNK/p38 activation.
"Based on in vivo and in vitro results from our adult mouse model, we suggest that paracrine effects induced by systemic transplantation of hASCs are the predominant mechanism mediating the therapeutic effects of hASCs in treatment of osteoporosis," write the researchers.
They conclude: "Collectively, hASCs transplanted via the circulatory system could function as antiresorptive and anabolic agents, and could be a valuable therapeutic option for treatment of both high-turnover and low-turnover osteoporosis."
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By Laura Dean