HEALTH NEWS

Study Title:

Bone Loss Caused by Free Radicals

Study Abstract

Aging leads to the disruption of the homeostatic balance of multiple biological systems. In bone marrow multipotent mesenchymal cells undergo differentiation into various anchorage-dependent cell types, including osteoblasts and adipocytes. With age as well as with treatment of antidiabetic drugs such as thiazolidinediones, mesenchymal cells favor differentiation into adipocytes, resulting in an increased number of adipocytes and a decreased number of osteoblasts, causing osteoporosis. The mechanism behind this differentiation switch is unknown. Here we show an age-related decrease in the expression of Maf in mouse mesenchymal cells, which regulated mesenchymal cell bifurcation into osteoblasts and adipocytes by cooperating with the osteogenic transcription factor Runx2 and inhibiting the expression of the adipogenic transcription factor Pparg. The crucial role of Maf in both osteogenesis and adipogenesis was underscored by in vivo observations of delayed bone formation in perinatal Maf–/– mice and an accelerated formation of fatty marrow associated with bone loss in aged Maf+/– mice. This study identifies a transcriptional mechanism for an age-related switch in cell fate determination and may provide a molecular basis for novel therapeutic strategies against age-related bone diseases.

From press release:

Recent data have suggested that the imbalance between bone formation and bone destruction that causes osteoporosis is a result of a decrease in formation of bone forming osteoblast cells from mesenchymal cells upon aging. New research in mice provides insight into this decrease and might provide new avenues of research for those developing approaches to treat age-related osteoporosis.

Aging disrupts the balance between bone formation and bone destruction, resulting in osteoporosis, which is characterized by reduced bone mass and increased risk of fracture. Recent data have suggested that this imbalance is a result of a decrease in formation of bone forming osteoblast cells from mesenchymal cells upon aging. Instead, these cells form more fat cells. Insight into this age-related switch in cell type generation has now been provided by a team of researchers, led by Hiroshi Takayanagi, at Tokyo Medical and Dental University, Japan, working in mice.

The data generated might provide new avenues of research for those developing approaches to treat age-related osteoporosis.

In the study, the gene regulatory protein Maf was found to promote mesenchymal cell generation of osteoblasts and suppress their generation of fat cells. Consistent with this, mice lacking Maf showed delayed bone formation. Furthermore, Maf levels were found to decrease in mouse mesenchymal cells upon aging and to be reduced by increased oxidative stress, something that occurs upon aging. Both the authors and, in an accompanying commentary, Laurie McCauley, at University of Michigan, Ann Arbor, believe these data could lead to new approaches to treat age-related osteoporosis.

Study Information

1.Keizo Nishikawa, Tomoki Nakashima, Shu Takeda, Masashi Isogai, Michito Hamada, Ayako Kimura, Tatsuhiko Kodama, Akira Yamaguchi, Michael J. Owen, Satoru Takahashi, Hiroshi Takayanagi.
Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation.
Journal of Clinical Investigation
2010 September
Tokyo Medical and Dental University, Japan.