Understanding Osteoporosis: Human Bone Density, Genetic Mechanisms, Gut Microbiota, and Future Prospects

Ahire, Jayesh J.; Kumar, Vikram; Rohilla, Alka

doi:10.1007/s12602-023-10185-0

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…Under physiological conditions, bone resorption and formation are in a dynamic equilibrium. The occurrence of OP may be a result of the disruption in the balance between bone resorption and bone formation, potentially resulting in a decrease in bone mass [ 18 , 19 ]. LWDH pills have been highlighted to promote osteogenic differentiation, which is beneficial in maintaining bone homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

Zhao,

Liang,

Yang

et al. 2024

Pharmaceuticals

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Objective: The therapeutic efficacy and molecular mechanisms of traditional Chinese medicines (TCMs), such as Liuwei Dihuang pills (LWDH pills), in treating osteoporosis (OP) remain an area of active research and interest in modern medicine. This study investigated the mechanistic underpinnings of LWDH pills in the treatment of OP based on network pharmacology, bioinformatics, and in vitro experiments. Methods: The active ingredients and targets of LWDH pills were retrieved through the TCMSP database. OP-related targets were identified using the CTD, GeneCards, and DisGeNET databases. The STRING platform was employed to construct a protein–protein interaction (PPI) network, and core targets for LWDH pills in treating OP were identified. The GO functional and KEGG pathway enrichment analyses for potential targets were performed using the R package “clusterProfiler”. A “drug–target” network diagram was created using Cytoscape 3.7.1 software. The viability of MC3T3-E1 cells was evaluated using the CCK-8 method after treatment with various concentrations (1.25%, 2.5%, 5%, and 10%) of LWDH pill-medicated serum for 24, 48, and 72 h. Following a 48 h treatment of MC3T3-E1 cells with LWDH pill-medicated serum, the protein levels of collagen Ⅰ, RUNX2, Wnt3, and β-catenin were quantified using the Western blot analysis, and the activity of alkaline phosphatase (ALP) was measured. Results: A total of 197 putative targets for LWDH pills for OP treatment were pinpointed, from which 20 core targets were singled out, including TP53, JUN, TNF, CTNNB1 (β-catenin), and GSK3B. The putative targets were predominantly involved in signaling pathways such as the Wnt signaling pathway, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. The intervention with LWDH pill-medicated serum for 24, 48, and 72 h did not result in any notable alterations in the cell viability of MC3T3-E1 cells relative to the control group (all p > 0.05). Significant upregulation in protein levels of collagen Ⅰ, RUNX2, Wnt3, and β-catenin in MC3T3-E1 cells was observed in response to the treatment with 2.5%, 5%, and 10% of LWDH pill-medicated serum in comparison to that with the 10% rabbit serum group (all p < 0.05). Furthermore, the intervention with LWDH pill-medicated serum resulted in the formation of red calcified nodules in MC3T3-E1 cells, as indicated by ARS staining. Conclusions: LWDH pills may upregulate the Wnt/β-catenin signaling pathway to elevate the expression of osteogenic differentiation proteins, including collagen Ⅰ and RUNX2, and to increase the ALP activity in MC3T3-E1 cells for the treatment of OP.

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Section: Discussionmentioning

confidence: 99%

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

Zhao,

Liang,

Yang

et al. 2024

Pharmaceuticals

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“…Postmenopausal women are more likely to experience these problems [ 95 ]. Bone loss occurs in menopause as estrogens play a crucial role in the development and maintenance of bones [ 96 ]. Osteoporosis is a common condition, and many people are at high risk of having insufficient bone mass.…”

Section: Role In Other Diseasesmentioning

confidence: 99%

Unraveling the Puzzle: Health Benefits of Probiotics—A Comprehensive Review

Gul,

Durante-Mangoni

2024

JCM

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A growing number of probiotic-containing products are on the market, and their use is increasing. Probiotics are thought to support the health of the gut microbiota, which in turn might prevent or delay the onset of gastrointestinal tract disorders. Obesity, type 2 diabetes, autism, osteoporosis, and some immunological illnesses are among the conditions that have been shown to possibly benefit from probiotics. In addition to their ability to favorably affect diseases, probiotics represent a defense system enhancing intestinal, nutritional, and oral health. Depending on the type of microbial strain utilized, probiotics can have variable beneficial properties. Although many microbial species are available, the most widely employed ones are lactic acid bacteria and bifidobacteria. The usefulness of these bacteria is dependent on both their origin and their capacity to promote health. Probiotics represent a valuable clinical tool supporting gastrointestinal health, immune system function, and metabolic balance. When used appropriately, probiotics may provide benefits such as a reduced risk of gastrointestinal disorders, enhanced immunity, and improved metabolic health. Most popular probiotics, their health advantages, and their mode of action are the topic of this narrative review article, aimed to provide the reader with a comprehensive reappraisal of this topic matter.

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“…Other factors that may also contribute to OP risk and progression include periostin levels associated with endocrine disease [32], the gut microbiota [33,34], anti-Mullerian hormone [35,36], and genetic factors [37], reviewed in [38,39], and mediators such as irisin [40]. Vascular dysfunctions such as varicose veins have also been implicated in the development of OP [41].…”

Section: Variables and Factors Influencing Post-menopause Diseases An...mentioning

confidence: 99%

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

Hart

2024

IJMS

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For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications of childbirth. Thus, for much of evolution, many females did not reach the age of menopause (45–50 years of age) and it is mainly in the past several hundred years that the lifespan has been extended to >75 years, primarily due to public health advances, medical interventions, antibiotics, and nutrition. Therefore, the underlying biological mechanisms responsible for disease risk following menopause must have evolved during the complex processes leading to Homo sapiens to serve functions in the pre-menopausal state. Furthermore, as a primary function for the survival of the species is effective reproduction, it is likely that most of the advantages of having such post-menopausal risks relate to reproduction and the ability to address environmental stresses. This opinion/perspective will be discussed in the context of how such post-menopausal risks could enhance reproduction, with improved survival of offspring, and perhaps why such risks are preserved. Not all post-menopausal females exhibit risk for this set of diseases, and those who do develop such diseases do not have all of the conditions. The diseases of the post-menopausal state do not operate as a unified complex, but as independent variables, with the potential for some overlap. The how and why there would be such heterogeneity if the risk factors serve essential functions during the reproductive years is also discussed and the concept of sets of reversible epigenetic changes associated with puberty, pregnancy, and lactation is offered to explain the observations regarding the distribution of post-menopausal conditions and their potential roles in reproduction. While the involvement of an epigenetic system with a dynamic “modification-demodification-remodification” paradigm contributing to disease risk is a hypothesis at this point, validation of it could lead to a better understanding of post-menopausal disease risk in the context of reproduction with commonalities may also lead to future improved interventions to control such risk after menopause.

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Understanding Osteoporosis: Human Bone Density, Genetic Mechanisms, Gut Microbiota, and Future Prospects

Cited by 7 publications

References 56 publications

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

Liuwei Dihuang Pills Enhance Osteogenic Differentiation in MC3T3-E1 Cells through the Activation of the Wnt/β-Catenin Signaling Pathway

Unraveling the Puzzle: Health Benefits of Probiotics—A Comprehensive Review

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

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