The Endocrine Function of Osteocalcin Regulated by Bone Resorption: A Lesson from Reduced and Increased Bone Mass Diseases

Rossi, Michela; Battafarano, Giulia; Pepe, Jessica; Minisola, Salvatore; Fattore, Andrea Del

doi:10.3390/ijms20184502

Cited by 31 publications

(28 citation statements)

References 81 publications

(99 reference statements)

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“…IL-6 plays a key role in bone metabolism, and the increase of IL-6 level leads to bone loss. This may explain the increase of Dialister flora abundance in patients with PO (Rossi et al, 2019). In addition, the abundance of Dialister decreased in patients with rheumatoid arthritis and upper motor neuron intestinal syndrome after spinal cord injury (Gungor et al, 2016;Tito et al, 2017).…”

Section: Discussionmentioning

confidence: 95%

Gut Microbiome Reveals Specific Dysbiosis in Primary Osteoporosis

Xie

Sun

et al. 2020

Front. Cell. Infect. Microbiol.

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Object: Primary osteoporosis (PO) is the most common bone disease, which is characterized by decreased bone mass, damage of bone tissue microstructure, increased bone fragility, and is prone to fracture. Gut microbiome may be involved in bone metabolism of PO through gut-brain axis regulation of immune system and endocrine system, however, the specific mechanism is still unclear. The purpose of this study was to characterize the gut microbiome of patients with PO and its possible role in the occurrence and development of the disease. Methods: Fecal samples were collected from 48 PO patients and 48 healthy controls (HC). The composition of gut microbiome community was analyzed by 16s rDNA amplification sequencing, and the difference of gut microbiome composition between PO patients and HC individuals was compared. PICRUSt was also used to predict the biological function of gut microbiome in patients with PO, and to explore its possible role in the occurrence and development of this disease. The classification model is constructed by random forest algorithm so as to screen the key biomarkers. Result: The diversity of gut microorganisms in PO patients was significantly higher than that in HC group (p < 0.05) and there was significant difference in microbial composition in PO group. The abundance of Dialister (0.036 vs. 0.004, p < 0.001) and Faecalibacterium (0.331 vs. 0.132, p < 0.001) were significantly enriched which were the key flora related to PO. Although no significant correlation between bone mineral density and the richness of microbial communities are found, PICRUST results show that there are a wide range of potential pathways between gut microbiome and PO patients, including genetic information processing, metabolism, environmental information processing, cellular processes, human diseases, and organic systems. Notably, the discriminant model based on dominant microflora can effectively distinguish PO from HC (AUC = 93.56). Conclusions: The findings show that PO is related to the change of gut microbiome, especially the enriched Dialister and Faecalibacterium genera, which give new clues to understand the disease and provide markers for the diagnosis and new strategies for intervention treatment of the disease.

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Section: Discussionmentioning

confidence: 95%

Gut Microbiome Reveals Specific Dysbiosis in Primary Osteoporosis

Xie

Sun

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Across the ruffled border, protons and lysosomal degrading enzymes are transferred to the underlying bone to erode the bone matrix [ 7 ]. The secretion of protons by Vacuolar (V)-H+ATPase and Cl- by the chloride proton antiporter CLC-7 lowers the pH in the resorption lacuna to about 4.5, which leads to the demineralization of the bone matrix and unmasking the organic components mainly composed of type 1 collagen [ 8 , 9 , 10 ]. In the next step, exposed collagen and other organic components are degraded by lysosomal enzymes such as cathepsin K and MMPs (matrix metalloproteinases) released by the fusion of lysosomes with the ruffled border [ 11 , 12 , 13 ].…”

Section: Bone Remodelingmentioning

confidence: 99%

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

et al. 2020

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Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue.

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“…OCN signaling regulates the expression of genes that are associated with testosterone production in a cAMP response element binding protein (CREB)-dependent manner, as demonstrated by CREB phosphorylation in osteocalcin-treated Leydig cells and corroborated in Creb Leyding −/− mice [ 163 ]. Indeed, unOCN has been shown to activate GPRC6A using Docking simulation and in vitro assay with MA-10 and β-TC6 cell lines [ 165 ], inducing the PKA, PKC, PKG activation, as well as the Ca 2+ release [ 115 ], driving the specific expression of star , c yp11a , cyp17 , and 3 β -hsd genes that are required for testosterone biosynthesis, and representing a complex pancreas-bone-testis axis communication (reviewed in [ 162 , 166 ]). Interestingly, it was recently found that this regulation through OCN was LH independent in Sprague-Dawley male rats [ 167 ].…”

Section: The Impact Of Vitamin K In Reproductionmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.

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The Endocrine Function of Osteocalcin Regulated by Bone Resorption: A Lesson from Reduced and Increased Bone Mass Diseases

Cited by 31 publications

References 81 publications

Gut Microbiome Reveals Specific Dysbiosis in Primary Osteoporosis

Gut Microbiome Reveals Specific Dysbiosis in Primary Osteoporosis

The Role of Autophagy in Osteoclast Differentiation and Bone Resorption Function

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

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