Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis

Abstract

Objective. While the role of osteoclasts in bone loss has been well investigated, the involvement of osteoblast-lineage cells has not been completely elucidated. Several genes contribute to normal osteoblastic differentiation from mesenchymal stem cells (MSCs), but an understanding of their role in the pathogenesis of osteoporosis is still lacking. The present study was undertaken to evaluate a possible alteration of osteogenic gene expression as a mechanism contributing to bone loss.Methods. We studied the osteogenic differentiation process in MSCs obtained from the peripheral blood of 31 patients with osteoporosis and 20 normal donors. The cells were evaluated by colony-forming unit-fibroblastic assay and cultured in osteogenic medium to analyze the transcription factors runt-related transcription factor 2 (RUNX-2) and Sp7 and the bone-related genes COL1A1, SPARC, and SPP1 after 3, 8, and 15 days of differentiation. In addition, to determine possible differences between the 2 groups in terms of osteoclastic and osteoblastic activation, we quantified the osteoprotegerin (OPG) and RANKL levels in the supernatants of osteoblastic culture.Results. Circulating MSCs were increased in osteoporosis patients compared with normal donors. In contrast, gene expression analysis revealed downregulation of RUNX2, Sp7, COL1A1, SPARC, and SPP1 in patients with osteoporosis, associated with a lower OPG:RANKL ratio.Conclusion. These results suggest that an alteration of osteoblastic differentiation may contribute to the pathogenesis of osteoporosis. The noninvasive approach used in the present study could be proposed as a useful tool for studying mesenchymal involvement in bone diseases.

Senescence‐associated intrinsic mechanisms of osteoblast dysfunctions

“…Also, the number of Stro-1+ (a marker of the clonogenic CFU-F) did not change with age (Stenderup et al, 2001;Zhou et al, 2008). Interestingly, the number of peripheral-bloodderived CFU-f was found to increase in patients with osteoporosis compared to age-matched controls (Dalle Carbonare et al, 2009). While the discrepancies in the results reported in human studies may be related to differences in the methods employed, it can be generally concluded that the reported age-related decline in the number of MSC occurred in early adulthood after the termination of skeletal growth, with no further change afterward.…”

Stem cell therapy for inflammatory bowel disease

“…Autologous MSCs, on the contrary, would be favorable because they do not suffer from immune rejection. However, it is not clear whether autologous MSCs which are expanded from patients with inflammatory or autoimmune diseases may be fully functional [54]. Surprisingly, the therapeutic effects of MSCs do not depend on their full engraftment, but rely on the capacity of MSCs to inhibit pathogenic immune responses and to release trophic factors favoring tissue repair [55][56][57].…”

Influence of adipose tissue derived mesenchymal stem cells in combination with injectable bone substitute on osteoclastogenesis in osteoporotic rats

“…Evidence that OPG acts as an inhibitor of osteoclastogenesis has emerged from experiments with transgenic mice, in which over expression of OPG led to severe osteopetrosis and reduced the number of mature osteoclasts. In contrast, mice lacking the gene for OPG are osteoporotic (Dalle Carbonare et al, 2009). The biological effects of OPG include inhibition of the terminal stages of osteoclast differentiation and suppression of mature osteoclast activation (Kobayashi et al, 2009) by blocking the RANKL/RANK interaction which activates the osteoclast formation (Sherman, 2012).…”