Systemic Skeletal Disease Research Articles

The Role of Osteocalcin in Patients with Osteoporosis: A Systematic Review

Background: Osteoporosis is the most common systemic skeletal disease worldwide. We aimed to review the latest studies related to osteocalcin and osteoporosis to clarify this relationship more precisely. Methods: A systematic literature search was performed to review studies on the effects of osteocalcin on osteoporosis, on studied published between January 2013 and January 2023. We systematically reviewed Web of Science, PubMed, ProQuest, Scopus, and Google Scholar. Results: The search yielded 4903 records, including 1063 from PubMed, 2307 from Scopus, 1084 from Web of Science, 408 from ProQuest, and 41 from Google Scholar, and twelve articles were included for data extraction and quality assessment. A significant increase in the serum level of osteocalcin was observed in postmenopausal women with osteoporosis (P<0.05), and there was a negative correlation between bone mineral density and the serum level of osteocalcin. Conclusion: Osteocalcin could be a promising marker for the diagnosis and screening of patients with osteoporosis.

An Andrias davidianus derived composite hydrogel with enhanced antibacterial and bone repair properties for osteomyelitis treatment.

Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases.

Bazi Bushen attenuates osteoporosis in SAMP6 mice by regulating PI3K-AKT and apoptosis pathways.

Osteoporosis (OP), a systemic skeletal disease, is characterized by low bone mass, bone tissue degradation and bone microarchitecture disturbance. Bazi Bushen, a Chinese patented medicine, has been demonstrated to be effective in attenuating OP, but the pharmacological mechanism remains predominantly unclear. In this study, the senescence-accelerated mouse prone 6 (SAMP6) model was used to explore bone homeostasis and treated intragastrically for 9 weeks with Bazi Bushen. Invivo experiments showed that Bazi Bushen treatment not only upregulated the levels of bone mineral density and bone mineral content but also increased the content of RUNX2 and OSX. Furthermore, the primary culture of bone mesenchymal stem cells (BMSCs) in SAMP6 mice was used to verify the effects of Bazi Bushen on the balance of differentiation between osteoblasts and adipocytes, as well as ROS and aging levels. Finally, the pharmacological mechanism of Bazi Bushen in attenuating OP was investigated through network pharmacology and experimental verification, and we found that Bazi Bushen could significantly orchestrate bone homeostasis and attenuate the progression of OP by stimulating PI3K-Akt and inhibiting apoptosis. In summary, our work sheds light on the first evidence that Bazi Bushen attenuates OP by regulating PI3K-AKT and apoptosis pathways to orchestrate bone homeostasis.

Serum proinflammatory cytokines, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG ratio in mild and severe COVID-19

IntroductionOsteoporosis, a systemic skeletal disease, is characterized by a quantitative and qualitative, and progressive decrease in bone mass, which is related to inflammation. Since a cytokine storm is triggered in Coronavirus disease 2019 (COVID-19), this study aims to evaluate pro-inflammatory cytokines (TNF-α, IL-1β), Receptor activator of nuclear factor-κB ligand (RANKL)/serum osteoprotegerin (OPG) ratio, and their relationship in mild and severe COVID-19.MethodsThis study was performed on 48 adult patients (18 mild, 18 severe COVID-19, and 12 healthy subjects as a control group). Serum OPG, RANKL, TNF-α, IL-1β, 25-OH vitamin D, and ALKp were measured by ELISA and colorimetric assay.ResultsCOVID-19 patients had a significant increase in RANKL, and RANKL/OPG in mild and severe form (p < 0.001) while OPG decreased significantly in severe form compared to healthy controls (p < 0.05). Inflammatory cytokines (TNF-α and IL-1β) increased in both groups of patients whereas Alkaline phosphatase (ALKp) increased only in severe patients (p < 0.001). Both groups had 25-OH vitamin D deficiency in comparison to healthy ones (p < 0.001). Pearson’s correlation coefficient was performed to determine the relationship between RANKL, OPG, ALKp, and 25-OH vitamin D with TNF-α and IL-1β in mild and severe COVID-19, which was statistically significant.ConclusionSerum RANKL/OPG ratio was elevated in COVID-19 individuals and is assumed to be a risk factor for BMD reduction and osteoporosis in these patients. Correlations between IL-1β, TNF-α, ALKp, 25-OH vitamin D, OPG, RANKL, and RANKL/OPG ratio offered the potential role of these proinflammatory markers in the mechanism of osteoporosis in COVID-19 patients.

The role of short-chain fatty acids in the regulation of osteoporosis: new perspectives from gut microbiota to bone health: A review.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration, resulting in increased fracture risk. With an aging population, osteoporosis imposes a heavy burden worldwide. Current pharmacotherapies such as bisphosphonates can reduce fracture risk but have limitations. Emerging research suggests that gut microbiota regulates bone metabolism through multiple mechanisms. Short-chain fatty acids (SCFAs) produced from microbial fermentation of dietary fiber beneficially impact bone health. Preclinical studies indicate that SCFAs such as butyrate and propionate prevent bone loss in osteoporosis models by inhibiting osteoclastogenesis and immune modulation. Early clinical data also suggest that SCFA supplementation may improve bone turnover markers in postmenopausal women. SCFAs likely act via inhibition of osteoclast differentiation, stimulation of osteoblast activity, regulation of T cells, and other pathways. However, optimal dosing, delivery methods, and long-term safety require further investigation. Modulating the gut-bone axis via supplementation, prebiotics/probiotics, diet, and lifestyle interventions represents an innovative therapeutic approach for osteoporosis. Harnessing the interplay between microbiome, metabolism, immunity, and bone may provide new directions for managing osteoporosis in the future.

Probiotics: a promising intervention for osteoporosis prevention and management.

Osteoporosis (OP) is a systemic skeletal disease that is characterized by low bone mass and increased fracture risk. This article explores the potential of probiotics as an adjunctive approach for the prevention and management of OP. It has been well established that the gut microbiota (GM), a complex community of microbes, plays an important role in bone health. The gut dysbiosis is linked with a higher risk of OP. However, the consumption of probiotics in adequate amounts restores gut health thus improving bone health. Probiotics may influence bone metabolism through enhanced calcium absorption, reduced inflammation, and increased bone formation. The animal and human studies demonstrate the positive effects of probiotics on bone health parameters like reduced osteoclastogenesis, bone resorption markers, osteoblast, osteocyte apoptosis, and increased bone mineral density and expression of osteoprotegerin. The current evidence suggests that probiotics can be used as an adjunctive approach along with the existing therapies for the prevention and management of OP.

The Analysis of ECE1 and PPARG Variants in the Development of Osteopenia and Osteoporosis in Postmenopausal Women.

Osteoporosis is a multifactorial systemic skeletal disease that is characterized by a low bone mineral density (BMD) and the microarchitectural deterioration of bone tissue, leading to bone fragility. The search for new genes that may play an important role in the regulation of bone mass and the development of osteoporosis is ongoing. Recently, it was found that altering the activity of the endothelin-1-converting enzyme encoded by the ECE1 gene may affect bone mineral density (BMD). Another gene involved in the process of osteoblast differentiation and maturation is believed to be PPARG (peroxisome proliferator-activated receptor gamma). This participates in regulating the transformation of stem cells and affects the process of bone formation and resorption. Therefore, we analyzed the association of the ECE1 and PPARG variants with osteopenia and osteoporosis risk in the Polish population. This study included a group (n = 608) of unrelated Polish women (245 individuals with osteoporosis (aged: 57 ± 9), 109 individuals with osteopenia (aged: 53 ± 8) and 254 healthy controls (aged: 54 ± 8)). The real-time PCR technique was used to determine the genetic variants for rs213045 (-338G>T) and rs213046 (-839A>C) of the ECE1 gene and rs1801282 (Pro12Ala, C>G) of the PPARG gene. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, in the densitometric results, lower median Z-score values were observed for the T allele compared to the G allele for the rs213045 variant of the ECE1 gene (-1.11 ± 1.07 vs. -0.78 ± 1.21, p = 0.021). Moreover, the TT genotype for the rs213045 variant was more common in women with osteopenia (13.8%, OR = 2.82, p < 0.05) and osteoporosis (7.8%, OR = 1.38, p > 0.05) compared to the control group (5.5%). Additionally, our results suggested that the T allele of rs213045 was more common in women with osteopenia compared to the controls. We further observed that the haplotype containing two major GA alleles of ECE1 (rs213045, rs213046) could reduce the risk of osteopenia in our population. Finally, we found that women with osteoporosis had statistically significantly lower body mass and BMI values compared to the control group. Our results suggest that the ECE1 rs213045 variant may increase the risk of osteopenia. However, the data obtained require confirmation in further studies.

The MicroRNAs in the Pathophysiology of Osteoporosis.

Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis' development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted to the role that microRNA (miRNA) plays in osteoporosis regulation. A microRNA (miRNA) is a group of small single-stranded RNA molecules involved in regulating gene expression in eukaryotic organisms. As microRNAs (miRNAs) are key regulators of gene expression and can modulate processes related to bone metabolism, they have become increasingly important for studying osteoporosis pathogenesis. The available research suggests that miRNAs play an important role in regulating processes associated with bone metabolism, especially by influencing bone resorption and synthesis. Furthermore, microRNAs can also serve as potential therapeutic targets for osteoporosis, besides being a rapid and specific biomarker.

Forestier disease: A possible cause of decannulation failure

Diffuse Idiopathic Skeletal Hyperostosis (DISH) [1] also known as Forestier disease, is a noninflammatory, systemic skeletal disease of unknown aetiology. DISH is a common but underdiagnosed disease that is usually observed in elderly people and has been reported to affect up to 10% of patients over 65 years of age [2]. The diagnosis is primarily radiological characterised by the ossification of the anterior longitudinal ligament, with osteophytes formation along the spinal column of at least four contiguous vertebral bodies, a minimal degree of degenerative disc disease and absence of apophyseal joint ankylosis and sacroiliac joint fusion, erosions, or sclerosis [3]. DISH is usually asymptomatic but may compress the posterior wall of the aero digestive tract and lead to dysphagia, globus, hoarseness, stridor, dyspnea and neurological problems. Although dysphagia is not uncommon among the presenting symptoms of DISH, dysphonia and stridor are rarely reported. Cervical hyperostosis in patients with DISH is responsible for 17%-28% incidence of dysphagia, and about 8% of patients failed to respond to conservative treatment and surgical excision through an anterior cervical approach was required [3]. Many studies have been conducted on the surgical approach [4] and anaesthetic evaluation of patients with DISH [5]. Less known are the difficulties in weaning from the tracheostomy tube in these patients, especially when the diagnosis of DISH is unknown.

Systematical mutational analysis of teriparatide on anti-osteoporosis activity by alanine scanning

Osteoporosis is a progressive systemic skeletal disease that decreases bone density and bone quality, making them fragile and easy to break. In spite of effective anti-osteoporosis potency, teriparatide, the first anabolic medications approved for the treatment of osteoporosis, was proven to exhibit various side effects. And the relevant structure–activity relationship (SAR) of teriparatide was in need. In this work, we performed a systematical alanine scanning against teriparatide and synthesized 34 teriparatide derivatives. Their biological activities were evaluated and the importance of each residue for anti-osteoporosis activity was also revealed. A remarkable decrease in activity was observed for alanine replacement of the residue Gly12, His14, Ser17, Arg20 and Leu24, showcasing the important role of these residues in teriparatide on anti-osteoporosis activity. On contrary, when Gly13 and Gln30 were mutated to Ala, the peptide derivatives exhibited the significantly increased activities, demonstrating that these two residues could be readily replaced. Our research expanded the peptide library of teriparatide analogues and presented a potential opportunity for designing the more powerful anti-osteoporosis peptide agents.

Effect of Different Exercise Interventions on Grip Strength, Knee Extensor Strength, Appendicular Skeletal Muscle Index, and Skeletal Muscle Index Strength in Patients with Sarcopenia: A Meta-Analysis of Randomized Controlled Trials.

Sarcopenia is a systemic skeletal muscle disease that is more prevalent in older adults. The role of exercise in improving the disease has been demonstrated. However, due to the variety of exercise modalities, it is not clear what type of exercise provides the best benefit. The aim of this meta-analysis was to analyze the effects of different exercise modalities on grip strength, appendicular skeletal muscle index, skeletal muscle index, and knee extensor strength in elderly patients with sarcopenia. The protocol for this evaluation was registered on the PROSPERO website and the databases PubMed, WOS, Cochrane Library, and Embase were searched. Thirteen studies were included in the analysis. The results showed that exercise interventions had positive effects on grip strength and knee extension muscle strength, with resistance training being the most effective. There was no significant improvement in appendicular skeletal muscle index or skeletal muscle index. This study still has limitations. For example, age group and exercise duration were not considered. Future studies should further explore benefits in age groups as well as other relevant outcome indicators.

Awareness About Osteoporosis Among the General Population Based on the Osteoporosis Knowledge Assessment Tool (OKAT): A Cross-Sectional Study in the Northern Border Region of Saudi Arabia.

Osteoporosis is a progressive systemic skeletal disease characterized by increasing susceptibility to fractures. The current study was conducted to assess the awareness about osteoporosis among the general population in the Northern Border region of Saudi Arabia to improve awareness and proper planning for public awareness about osteoporosis. The study was conducted as across-sectional survey study, based on the online distribution of the Arabic-translated Osteoporosis Knowledge Assessment Tool (OKAT). The questionnaire questions cover the demographic characteristics of the participants, as well as symptoms, risk factors, prevention, and knowledge of treatment centers for osteoporosis in Saudi Arabia. 395 participants were enrolled in the study after their informed consenting. After scoring all correct answers for each participant, the mean score of all participants' answers was 12.5±3.4 (range 0-19). Participants with poor knowledge (0-7 scores), moderate knowledge (8-13 scores), and good knowledge (13-20 scores) represent 61 (15.4%), 213 (53.9%), and 121 (30.6%), respectively. The mean percentage of right answers to all the questions is 44.1%. The highest awareness level was shown in the area of osteoporosis symptoms and risk of fractures, while the lowest was recorded in the questions covering the risk factors. Ages, genders, jobs, and levels of education significantly affected the participants' levels of awareness. The public awareness among the population in the Northern Border region about osteoporosis is less than satisfactory. More awareness activities targeting the risky groups should be planned especially in the area of risk factors and preventive measures for osteoporosis.

Knowledge, Attitude, and Practices Towards Osteoporosis Among Adults in the United Arab Emirates (UAE) in 2023.

Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue. Osteoporosis is considered a burden to global economic, social, and health development. Osteoporosis exerts a substantial global influence, markedly influencing rates of illness and death on a broad scale. Clinical features of osteoporosis can include chronic back pain, loss of height, and a stooped posture, as well as an increased risk of fractures in the spine, hip, and wrist. Accurate identification and monitoring of these clinical features are essential for effective management and treatment of osteoporosis. This study aims to identify the knowledge, attitudes, and practices (KAP) of adults (over 18 years) about osteoporosis and identify relations between knowledge, attitudes, and practices with demographic data. Furthermore, to assess the risk factors and preventive measures for osteoporosis. Data from 446 responders were collected using a Google Forms questionnaire, including questions to assess knowledge, attitudes, and practice levels among adults 18 years and above in the United Arab Emirates (UAE). The collected data and statistical analysis were done through the IBM® SPSS® Statistics. Chi-Square was used in SPSS Statistics; the chi-square test was used for the relation between categorical variables, and P less than 0.05 was the cut-off level of significance. The research revealed that 41.9% of the participants had good knowledge, 38.8% had a positive attitude, and 45.3% had poor practices. The results also showed that there is a statistically significant correlation between gender and knowledge, attitudes, and practices. Our research demonstrates that there's a statistically significant correlation between gender variables with knowledge, attitudes, and practices. These findings have important implications in assessing the correlation between variables in our research that could be used to prevent osteoporosis further, target the specific demographic group, and provide the required education. Overall, our research contributes to a better understanding of the knowledge, attitude, and practices towards Osteoporosis among adults in the UAE and underscores the importance of further awareness in this area.

Apigenin alleviates osteoporosis by orchestrating SIRT1/HIF1α signaling in mesenchymal stem cells

Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and a degenerative bone microarchitecture. Apigenin (API), a flavonoid derived mainly from celery, has been reported to be beneficial for the treatment of OP; however, the underlying mechanisms remain unclear. Moreover, the effects of API on bone-forming cells, including mesenchymal stem cells and osteoblasts, remain unclear. In the present study, we first determined that API treatment could promote bone formation, improve bone metabolism in ovariectomized (OVX) mice, and effectively ameliorate bone loss, as supported by micro-CT scanning and histological staining of mouse femurs. In vitro investigations have confirmed that API has a bidirectional regulatory effect on bone metabolism, promoteing osteogenic differentiation and inhibiting osteoclastogenesis. The further study displayed that the promotion of osteogenesis of bone marrow-derived mesenchymal stem cells from OVX mice mainly through regulating SIRT1 and its downstream HIF1α signaling. In summary, API treatment may be a novel and promising therapeutic strategy for the treatment of OP.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

Оптимизация восстановления костной ткани у больных ревматоидным артритом и остеопорозом, осложненным переломами

The article provides a brief summary of bone remodeling, including its stages, disorders, and correction. Osteoporosis (OP) is a systemic skeletal disease in which bone resorption predominates over bone formation. OP is characterized by a decrease in bone mass and density, as well as a disturbance of bone microarchitecture. This leads to a decrease in bone strength and an increased risk of fractures. This paper describes a case of a woman with rheumatoid arthritis (RA) and OP complicated by low-trauma fractures. The authors emphasize that OP is a multifactorial disease and one of the most common bone diseases, particularly among the elderly. OP in RA is an immune- mediated secondary osteopathy and is considered both a comorbidity and complication of the underlying disease. Patients with RA have a higher bone mineral density (BMD) and a higher rate of fractures than the general population. Fractures can occur in individuals with osteopenia or normal BMD values. Therefore, it is important to carefully analyze the risk factors for OP and fractures when planning RA therapy. The ‘treat to target' strategy aims to achieve RA remission or reduce disease activity while also preventing complications, such as osteoporotic fractures. To manage bone metabolism disorders in patients with RA who also have osteoporosis and fractures, it is necessary to control RA activity and prescribe basic therapy for osteoporosis, such as ossein-hydroxyapatite complex and alfacalcidol, as well as pathogenic drugs that prevent bone resorption. Additionally, patients with osteoporosis and fractures require pain-reducing measures, restorative treatment, and rehabilitation. Effective management requires a multidisciplinary approach involving physicians from various specialties. KEYWORDS: bone tissue structure, resorption, rheumatoid arthritis, osteoporosis, fractures, pharmacotherapy of bone metabolism disorders, ossein-hydroxyapatite complex. FOR CITATION: Dydykina I.S., Kovalenko P.S., Kudinskiy D.M., Kovalenko A.A., Ivanova M.E. Optimizing bone repair in patients with rheumatoid arthritis and osteoporosis complicated by fractures. Russian Medical Inquiry. 2024;8(2):94–101 (in Russ.). DOI: 10.32364/2587- 6821-2024-8-2-7.

The role of circulating miRNAs in the diagnosis of osteoporosis miRNAs in osteoporosis.

Osteoporosis, defined as a systemic skeletal disease, is characterized by increased bone fragility and fracture risk. Studies have shown that dysregulation of the functions of miRNAs or the mechanisms they mediate may be an important pathological factor in bone degeneration. Therefore, the aim of the study was to determine the role of miRNAs, which are thought to play a role in bone metabolism, in osteoporosis. The study included 48 patients who were diagnosed with osteoporosis according to the results of a bone mineral density assessment by quantitative computed tomography and 36 healthy individuals. MiRNAs from plasma samples obtained from blood samples taken into ethylenediaminetetraacetic acid (EDTA) tubes were isolated with the miRNA isolation kit and converted to cDNA. Expression analysis of miR-21-5p, miR-34a-5p, miR-210, miR-122-5p, miR-125b-5p, miR-133a, miR-143-3p, miR-146a, miR-155-5p, and miR-223 was performed on the real-time PCR (RT-PCR) device. When miRNA expression levels in the patient group were compared with the control group, all miRNAs were found to be downregulated in the patients. When fold changes in expression levels in the patient group were examined, significant differences were found in miR-21-5p, miR-133a, mir143-3p, miR-210, and miR-223. In the receiver operating curve analysis, area under the curve=0.882 for the combination of miR-34, miR-125, miR-133, and miR-210. In this study, it was determined that the combined effects of miRNAs, as well as their single effects, were effective in the development of osteoporosis. Therefore, a miRNA panel to be created can make a significant contribution to the development of novel diagnostic and treatment approaches for this disease.

Hypermethylation of Bmp2 and Fgfr2 Promoter Regions in Bone Marrow Mesenchymal Stem Cells Leads to Bone Loss in Prematurely Aged Mice.

Osteoporosis is an age-related, systemic skeletal disease that poses a significant public health challenge in contemporary society. Development at the epigenetic level is emerging as an important pathogenic mechanism of osteoporosis. Despite indications of a robust association between DNA methylation and osteoporosis development, a comprehensive understanding of the specific role of DNA methylation in osteoporosis remains limited. In this study, significant bone loss was detected at the beginning of eight weeks of age in mouse models of premature aging (SHJHhr mice). We identified a notable upregulation of DNA methyltransferase 3b/3l (Dnmt3b/l) and downregulation of ten eleven translocation dioxygenase 1 (Tet1) in bone marrow mesenchymal stem cells (BMSCs) isolated from SHJHhr mice, along with an increase in the overall 5-methylcytosine (5mC) levels. Moreover, methylation capture sequencing revealed genomic hypermethylation in SHJHhr mice BMSCs. Integrated methylome and transcriptome analyses revealed several crucial methylated genes and networks that are potentially associated with osteoporosis development. Notably, elevated methylation levels of genes linked to the Wnt signaling pathway, particularly bone morphogenetic protein 2 (Bmp2) and fibroblast growth factor receptor (Fgfr2), appeared to compromise the osteogenic differentiation potential of BMSCs. Concurrently, DNA methyltransferase inhibitors attenuated the methylation of the promoter regions of Bmp2 and Fgfr2 and rescued the osteogenic differentiation potential of the BMSCs from SHJHhr mice. In summary, our study provides novel insights into the role of DNA methylation in the development of osteoporosis and suggests promising prospects for employing epigenetic interventions to manage osteoporosis.

Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction.

Sarcopenia is a systemic skeletal muscle disease characterized by a decline in skeletal muscle mass and function. Originally defined as an age-associated condition, sarcopenia presently also encompasses muscular atrophy due to various pathological factors, such as intensive care unit-acquired weakness, inactivity, and malnutrition. The exact pathogenesis of sarcopenia is still unknown; herein, we review the pathological roles of the neuromuscular junction and mitochondria in this condition. Sarcopenia is caused by complex and interdependent pathophysiological mechanisms, including aging, neuromuscular junction impairment, mitochondrial dysfunction, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, and inflammation. Among these, neuromuscular junction instability and mitochondrial dysfunction are particularly significant. Dysfunction in neuromuscular junction can lead to muscle weakness or paralysis. Mitochondria, which are plentiful in neurons and muscle fibers, play an important role in neuromuscular junction transmission. Therefore, impairments in both mitochondria and neuromuscular junction may be one of the key pathophysiological mechanisms leading to sarcopenia. Moreover, this article explores the structural and functional alterations in the neuromuscular junction and mitochondria in sarcopenia, suggesting that a deeper understanding of these changes could provide valuable insights for the prevention or treatment of sarcopenia.