Reduced Expression of Interleukin-11 in Bone Marrow Stromal Cells of Senescence-Accelerated Mice (SAMP6): Relationship to Osteopenia with Enhanced Adipogenesis

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Abstract
Aging is associated with an increase in bone marrow adipose tissue and a reduction in bone turnover. The P6 strain of senescence‐accelerated mice (SAM) exhibit an early decrease in bone mass with a reduction in bone remodeling. In the bone marrow, suppressed osteoblastogenesis and osteoclastogenesis with enhanced adipogenesis are observed. The present study was undertaken to clarify the mechanism of age‐related changes in bone turnover using bone marrow cells from SAMP6 mice. Because interleukin (IL)‐11 has been shown to potently inhibit adipogenesis and to stimulate osteoclast formation, the effect of IL‐11 on the differentiation of bone marrow cells was examined. The impaired formation of both osteoblasts and osteoclasts was restored and the enhanced formation of adipocytes was suppressed by the addition of 10 pM recombinant human IL‐11. Other cytokines that activate gp130 as a common signal transducer, IL‐6 and leukemia inhibitory factor, did not have such effects. Sequence analysis of the entire coding region of IL‐11 cDNA obtained from SAMP6 stromal cells revealed no mutations. Constitutively secreted IL‐11 protein into culture media, and its mRNA expression stimulated by transforming growth factor β were reduced in stromal cells from SAMP6 compared with those in control mice. These results demonstrate that the expression of IL‐11 is reduced in bone marrow cells of SAMP6 and suggest that the reduction in IL‐11 actions is involved in the impairment of both osteoblastogenesis and osteoclastogenesis in these mice. There is a possibility that alterations in IL‐11 actions may be associated with the age‐related impairment in bone metabolism.

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