Journal
JOURNAL OF ENDOCRINOLOGY
Volume 226, Issue 3, Pages 121-134Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-14-0657
Keywords
osteoporosis; estrogen; iron; osteoclasts; oxidative stress
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Funding
- National Natural Science Foundation of China [81273090, 81302438]
- Jiangsu Provincial Grant [BL2014044]
- Study on the Project Application of Suzhou [LCZX210305]
- Science and Technology Projects of Suzhou [SS201327]
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Postmenopausal osteoporosis is a metabolic disease associated with estrogen deficiency. The results of numerous studies have revealed the positive correlation between iron accumulation and postmenopausal osteoporotic status. Although the results of previous studies have indicated that estrogen or iron alone have an effect on bone metabolism, their combined effects are not well defined. Using an in vivo mouse model, we found that bone mass was minimally affected by an excess of iron in the presence of estrogen. Once the source of estrogen was removed ( ovariectomy), iron accumulation significantly decreased bone mass. These effects were accompanied by fluctuations in the level of oxidative stress. To determine whether these effects were related to bone formation or bone resorption, primary osteoblasts (OBs), RAW264.7 cells, and bone-marrow-derived macrophages were used for in vitro experiments. We found that iron accumulation did inhibit the activity of OBs. However, estrogen had little effect on this inhibition. In contrast, iron promoted osteoclast differentiation through the production of reactive oxygen species. Estrogen, a powerful reactive oxygen scavenger, suppressed this effect in osteoclasts. Our data provided direct evidence that iron affected the bone mass only in the absence of estrogen. The inhibitory effect of estrogen on iron-induced osteopenia was particularly relevant to bone resorption rather than bone formation.
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