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A Possible Role for Sirtuin 7 in Osteoporosis

Researchers recently provided evidence to suggest that sirtuin 7 is involved in the imbalance between bone creation and and bone destruction that arises in old age, leading to osteoporosis. The extracellular matrix of bone tissue is constantly remodeled, with osteoclast cells breaking it down and osteoblast cells building it up. In older people the activity of osteoclasts begins to outweigh the activity of osteoblasts, weakening bones. There are many possible contributing causes, from the effects of inflammation on the generation of these cells to altered signaling environments in aged tissue affecting the pace at which the cells undertake work. Overall it has the look of a condition in which the proximate cellular cause of imbalanced bone remodeling is a fair way downstream from the roots of aging.

Bone is a living tissue that is repeatedly broken down (bone resorption) and remade (bone formation) little by little every day. If this balance collapses and bone resorption exceeds bone formation, bone density decreases and can lead to osteoporosis. Sirtuins are enzymes that play important roles in controlling aging, stress responses, various areas of the metabolism, and several other body functions. In mammals, there are seven types of sirtuins, SIRT1 to SIRT7. Although SIRT7 has been reported to be involved in cancer and lipid metabolism, its role in bone tissue and bone aging was unknown.

Recent experiments showed that mice lacking the SIRT7 gene had reduced bone mass. Analysis showed that bone formation and the number of osteoblasts (bone-building cells) had been reduced. Furthermore, the researchers obtained similar results using osteoblast-specific SIRT7 deficient mice, thereby showing that osteoblast-specific SIRT7 is important for bone formation. To clarify the mechanism, the researchers compared sirtuin (SIRT1, 6, and 7) expression in the skeletal tissue of young and old mice, and found that SIRT7 decreased with age. Additionally, the expression of genes indicating osteoblast differentiation was also decreased, thereby revealing that SIRT7 controls the differentiation of osteoblasts.

Researchers found that the transcription activity of SP7 (also known as Osterix), a protein known to induce differentiation of pre-osteoblasts into mature osteoblasts and osteocytes, was markedly decreased in osteoblasts that lacked the SIRT7 gene. "In situations where SIRT7 does not work sufficiently, such as in an older individual, osteoblast formation is impaired due to low SP7/Osterix transcriptional activity. We believe that this decreased osteogenesis is associated with osteoporosis. Our results show that the regulatory pathway of SIRT7 - SP7 / Osterix is a promising target for new therapeutic agents to treat decreased osteogenesis and osteoporosis."

Link: https://www.eurekalert.org/pub_releases/2018-09/ku-bon090318.php

Comments

"Highlights
The gut microbiome influences bone formation, most notably by affecting osteoclast differentiation.
Alterations in the gut microbiome are involved in osteoporosis.
The gut microbiome acts on bone tissue via complex mechanisms that include hormone level changes, T-cell activation and modifications in cytokine production."

https://www.sciencedirect.com/science/article/pii/S1297319X18300617

Posted by: Lee at September 18th, 2018 7:19 AM

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