Regulation Of Bone Health Research Articles

Regulation of bone health through physical exercise: Mechanisms and types.

Osteoporosis, characterized by bone mineral density reduction, bone mass loss, increased bone fragility, and propensity to fractures, is a common disease in older individuals and one of the most serious health problems worldwide. The imbalance between osteoblasts and osteoclasts results in the predominance of bone resorption and decreased bone formation. In recent years, it has been found that regular and proper exercise not only helps prevent the occurrence of osteoporosis but also adds benefits to osteoporosis therapy; accordingly, bone homeostasis is closely associated with mechanical stress and the intricate crosstalk between osteoblasts and osteoclasts. In this review, we summarize the mechanisms of exercise on osteoporosis and provide new proposals for the prevention and treatment of osteoporosis.

Soybean Meal-Dependent Acute Intestinal Inflammation Delays Osteogenesis in Zebrafish Larvae.

Foods are known to be modulators of inflammation and skeletal development. The intestine plays an essential role in the regulation of bone health mainly through the regulation of the absorption of vitamin D and calcium; in fact, inflammatory bowel diseases are often related to bone health issues such as low bone mineral density, high fracture risk, osteoporosis and osteopenia. Considering the complexity of the pathways involved, the use of a simple animal model can be highly useful to better elucidate the pathogenic mechanisms. Soybean flour with a high saponin content has been used in many studies to induce intestinal inflammation in zebrafish larvae. Using a 50% soybean meal (SBM), we analyzed the effects of this soy-induced inflammatory bowel disease on zebrafish larval osteogenesis. Soybean meal induces intestinal functional alterations and an inflammatory state, highlighted by neutral red staining, without altering the general development of the larvae. Our data show that the chondrogenesis as well as endochondral ossification of the head of zebrafish larvae are not affected by an SBM-diet, whereas intramembranous ossification was delayed both in the head, where the length of the ethmoid plate reduced by 17%, and in the trunk with a delayed vertebral mineralization of 47% of SBM larvae. These data highlight that diet-dependent bowel inflammation can differently modulate the different mechanisms of bone development in different zones of the skeleton of zebrafish larvae.

Enteropathogenic Escherichia coli Mediates CoCrMo Particle-Induced Peri-Implant Osteolysis by Increasing Peripheral 5-HT.

The human gut microbiota has been proven to have great effects on the regulation of bone health. However, the association between gut microbiota and particle-induced osteolysis, which is the primary cause of aseptic loosening, is still unknown. In this study, we used a combination of wide-spectrum antibiotics to eliminate the majority of gut microbiota and found that reduction of gut commensal bacteria significantly alleviated the progression of osteolysis, in which anaerobe was the biggest culprit in the exacerbation of osteolysis. Furthermore, colonization of enteropathogenic Escherichia coli (EPEC), a subspecies of anaerobe, could promote the development of particle-induced osteolysis by increasing the secretion of peripheral 5-hydroxytryptamine (5-HT) from the colon. Elevated 5-HT level decreased the phosphorylation of CREB and inhibited the proliferation of osteoblasts. Collectively, these results indicated EPEC colonization suppressed the bone formation and aggravated particle-induced osteolysis in vivo. Thus, clearance of EPEC is expected to become a potential preventive approach to treat debris-induced osteolysis and aseptic loosening.

M6A Methylation Regulates Osteoblastic Differentiation and Bone Remodeling.

Osteoporosis is a prevalent bone disease of the aging population, which is characterized by a decrease in bone mass because of the imbalance of bone metabolism. Although the prevention and treatment of osteoporosis have been explored by different researchers, the mechanisms underlying osteoporosis are not clear exactly. N6 methyladenosine (m6A) is a methylated adenosine nucleotide, which functions through its interaction with the proteins called “writers,” “readers” and “erasers.” The epigenetic regulation of m6A has been demonstrated to affect mRNA processing, nuclear export, translation, and splicing. At the cellular level, m6A modification has been known to affect cell proliferation, differentiation, and apoptosis of bone-related cells, such as bone marrow mesenchymal stem cells (BMSC), osteoblasts, and osteoclasts by regulating the expression of ALP, Runx2, Osterix, VEGF, and other related genes. Furthermore, PTH/Pth1r, PI3K‐Akt, Wnt/β‐Catenin, and other signaling pathways, which play important roles in the regulation of bone homeostasis, are also regulated by m6A. Thus, m6A modification may provide a new approach for osteoporosis treatment. The key roles of m6A modification in the regulation of bone health and osteoporosis are reviewed here in this article.

Vitamin D and sleep duration: Is there a bidirectional relationship?

Vitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

Osteoimmunology: The Regulatory Roles of T Lymphocytes in Osteoporosis.

Immune imbalance caused bone loss. Osteoimmunology is emerging as a new interdisciplinary field to explore the shared molecules and interactions between the skeletal and immune systems. In particular, T lymphocytes (T cells) play pivotal roles in the regulation of bone health. However, the roles and mechanisms of T cells in the treatment of osteoporosis are not fully understood. The present review aims to summarize the essential regulatory roles of T cells in the pathophysiology of various cases of osteoporosis and the development of T cell therapy for osteoporosis from osteoimmunology perspective. As T cell-mediated immunomodulation inhibition reduced bone loss, there is an increasing interest in T cell therapy in an attempt to treat osteoporosis. In summary, the T cell therapy may be further pursued as an immunomodulatory strategy for the treatment of osteoporosis, which can provide a novel perspective for drug development in the future.

Vitamin B<sub>12</sub> as a Regulator of Bone Health

In the early 1920s, the anti-anaemic effect of liver-rich diet had been recognized. The anti-anaemic substance from the liver was isolated by 1950 and called ‘vitamin B 12 ’ (hereafter B 12 ). It took another 20 years to structurally define and chemically synthesize B 12 in its pure form. Since then, it has been recognized that B 12 modulates a variety of biological systems, from immune system to bone homeostasis. Recent clinical studies have shown that B 12 deficiency is likely to be an important etiological factor in the pathogenesis of bone degeneration. In this regard, either observational studies that aimed to verify an association between low B 12 level and bone mass, or clinical trials on the effect of B 12 as a supplementary treatment in low bone mass patients have been presented in the emerging clinical literature. Recently, we created a mouse genetic model of B 12 deficiency to elucidate its mode of action by genetic deletion of gastric intrinsic factor, a protein essential for the absorption of B 12 from the gut. This has led to the identification of a novel gut–liver-bone axis that has the potential to be pharmacologically targeted for treating low bone mass diseases in humans. In this review, we revisit the history of B 12 from its discovery in the early 20th century to the elucidation of its mode of action in the bone till date.