Estrogen regulation of myokines that enhance osteoclast differentiation and activity

Abstract

Osteoporosis and sarcopenia are maladies of aging that negatively affect more women than men. In recent years, it has become apparent that bone and muscle are coupled not only mechanically as muscle pulls on bone, but also at a higher level with myokines, biochemical and molecular signaling occurring between cells of the two tissues. However, how estrogen deficiency in females impacts the chemical crosstalk between bone and muscle cells is not understood. We hypothesize that changes in estrogen signaling alters myokine expression and intensifies bone loss in women. In our present study, we demonstrate that conditioned media from ovariectomized or skeletal muscle deficient in estrogen receptor α (ERα) expression enhances osteoclast differentiation and activity. Using a cytokine array, we identified myokines that have altered expressions in response to loss of estrogen signaling in muscle. Lastly, we demonstrate that conditional deletion of ERα in skeletal muscle results in osteopenia due to an increase in the osteoclast surface per bone surface. Our results suggest that estrogen signaling modulates expression of myokines that regulate osteoclast differentiation and activity.

An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

“…This ultrastructural injury was also in accord with the top enriched GO_BP terms. These findings confirmed that estrogen insufficiency impaired the structure and function of skeletal muscle, in agreement with similar researches ( 8 , 45 , 46 ). Moreover, decreased expression of ER-β showed evidence for the impaired estrogen-ER signaling, and we subsequently obtained the corresponding results of down-regulated expression of ESRRG (Estrogen-related Receptor Gamma) (log2FC -1.046)) and the estrogen signaling pathway, which possibly accounted for the consequent histologic findings of myofibers.…”

“…The hormone-related sarcopenia shares similar characters with the age-related sarcopenia. Nevertheless, postmenopausal women take more risks of musculoskeletal disorders than men of the same age ( 46 – 48 ). Current clinical treatments for sarcopenia are limited to exercise and diet intervention and quite deficient in medicine ( 34 , 49 , 50 ).…”

Regulation of bone health through physical exercise: Mechanisms and types

“…Postmenopausal osteoporosis due to decreased estrogen levels and ovariectomized models show the characteristics of reduced estrogen levels ( 76 ). A recent study has demonstrated that estrogen signaling regulates expression and secretion of myokines that modulate osteoclast differentiation and activity.…”

“…A recent study has demonstrated that estrogen signaling regulates expression and secretion of myokines that modulate osteoclast differentiation and activity. The authors used conditioned media that were collected from ovariectomized and skeletal muscle deficient in estrogen receptor α expression mice, with cytokine array, and found that estrogen deficiency altered myokines levels ( 76 ).…”

The critical impact of traumatic muscle loss on fracture healing: Basic science and clinical aspects

“…Neighboring muscle interacts not only mechanically with bone but also through biochemical pathways and mediators 9–12 . For example, paracrine signals known as myokines (cytokines produced by muscle) and osteokines (cytokines produced by bone) mediate the crosstalk between these two tissues 9 .…”