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Paper of the Month

Paper of the Month: December 2020

Increased marrow adipogenesis does not contribute to age-dependent appendicular bone loss in female mice      

Aging Cell, 2020. doi: 10.1111/acel.13247

Marrow adipocytes and osteoblasts differentiate from common mesenchymal progenitors in a mutually exclusive manner, and diversion of these progenitors toward adipocytes in old age has been proposed to account for the decline in osteoblasts and the development of involutional osteoporosis. This idea has been supported by evidence that thiazolidinedione (TZD)-induced activation of PPARγ, the transcription factor required for adipocyte differentiation, increases marrow fat and causes bone loss. We functionally tested this hypothesis using C57BL/6J mice with conditional deletion of PPARγ from early mesenchymal progenitors targeted by the Prx1-Cre transgene. Using a longitudinal littermate-controlled study design, we observed that PPARγ is indispensable for TZD-induced increase in marrow adipocytes in 6-month-old male mice, and age-associated increase in marrow adipocytes in 22-month-old female mice. In contrast, PPARγ is dispensable for the loss of cortical and trabecular bone caused by TZD or old age. Instead, PPARγ restrains age-dependent development of cortical porosity. These findings do not support the long-standing hypothesis that increased marrow adipocyte differentiation contributes to bone loss in old age but reveal a novel role of mesenchymal cell PPARγ in the maintenance of cortical integrity.

Paper proposed by Eleni Douni