Mineralocorticoid receptor is a key factor in bone health, study finds

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The mineralocorticoid receptor has been discovered to be a key factor in aging bone health, according to new research out of the Medical College of Georgia at Augusta University. 

According to a study published in Journal of Bone and Mineral Research, drugs that block that receptor, such as hypertension medications, may help protect bone cells.

Prednisone is a glucocorticoid, best known for reducing inflammation, but in aging it can disrupt the healthy process of bone being made and destroyed, according to researchers.

While natural glucocorticoid levels increase with age, bone has more glucocorticoid receptors than mineralocorticoid receptors, according to Meghan E. McGee-Lawrence, PhD, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia. Glucocorticoids can coax stem cells to make bone-forming osteoblasts, but it also causes those osteoblasts to store more fat, and too much fat in the bone typically correlates with bone loss.

The MCG scientists found that the loss of functioning glucocorticoid receptors did not protect against bone loss in younger mice on calorie-restricted diets. There was increased fat accumulation in the bone marrow and worsened osteoporosis.

They also found that the mice had a smaller muscle mass, chose to move around less than mice typically do, and had higher blood pressure. The research also revealed that when they used drugs to inhibit the mineralocorticoid receptor, many of the problems were reversed.

“I think what it means is if we want to understand what these endogenous glucocorticoids, are doing we cannot just think about signaling through one receptor,” McGee-Lawrence said. “We thought that knocking out the glucocorticoid receptor would make things better, but it made them worse. We think the mineralocorticoid receptor may explain a lot of what is going wrong in aging bone.”

McGee-Lawrence and her team already have some evidence that bone’s expression of mineralocorticoid receptors goes up, potentially significantly, as a person ages. But they have early mixed results on whether glucocorticoid receptors go down with age and are exploring more about what happens with both receptor levels as well as learning more about the role of mineralocorticoid receptors in aging bone.