RESUMO
Osteoporosis is a clinical disease characterized by decreased bone density due to a disrupted balance between bone formation and resorption, which increases fracture risk and negatively affects the quality of life of a patient. LncRNAs are RNA molecules over 200 nucleotides in length with non-coding potential. Many studies have demonstrated that numerous biological processes involved in bone metabolism are affected. However, the complex mechanisms of action of lncRNAs and their clinical applications in osteoporosis have not yet been fully elucidated. LncRNAs, as epigenetic regulators, are widely involved in the regulation of gene expression during osteogenic and osteoclast differentiation. LncRNAs affect bone homeostasis and osteoporosis development through different signaling pathways and regulatory networks. Additionally, researchers have found that lncRNAs have great potential for clinical application in the treatment of osteoporosis. In this review, we summarize the research results on lncRNAs for clinical prevention, rehabilitation treatment, drug development, and targeted therapy for osteoporosis. Moreover, we summarize the regulatory modes of various signaling pathways through which lncRNAs affect the development of osteoporosis. Overall, these studies suggest that lncRNAs can be used as novel targeted molecular drugs for the clinical treatment of osteoporosis to improve symptoms.
Assuntos
Osteoporose , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Qualidade de Vida , Osteoporose/tratamento farmacológico , Osteoporose/genética , Osteogênese/genética , Osso e Ossos/metabolismo , Diferenciação CelularRESUMO
Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation. However, the role of IRE1α-TXNIP and its interaction with CK are still unclear. In this study, we examined the role and mechanism of action of CK in OA. We found that CK ameliorated OA and ERS in IL-1ß-treated chondrocytes and a monoiodoacetate-induced rat OA model. The effect of CK on inflammation, pyroptosis, and ERS was blocked by the ERS inducer tunicamycin. In conclusion, CK hindered OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis. Overall, our data indicate that CK could be useful in the treatment of OA and other chronic inflammatory diseases.
Assuntos
Osteoartrite , Proteínas Serina-Treonina Quinases , Ratos , Animais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Condrócitos , Apoptose , Estresse do Retículo Endoplasmático , Inflamassomos , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Osteoartrite/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacologiaRESUMO
Osteoblast proliferation and osteogenic differentiation (OGD) are regulated by complex mechanisms. The roles in cell proliferation and OGD of RNA-binding proteins in the insulin-like growth factor 2 mRNA-binding protein (IGF2BP) family remain unclear. To elucidate this, we examined the differential expression of IGF2BP2 in OGD and osteoporosis, and the expression profile of IGF2BP2-binding RNA in vitro. We screened the GEO database for differential expression of IGF2BP in OGD and osteoporosis, and verified the RNAs interacting with IGF2BP2 via RNA immunoprecipitation sequencing assays. The proliferation and OGD of IGF2BP2- and serum response factor (SRF)-treated cells, and their regulatory mechanisms, were examined. IGF2BP2 was differentially expressed in OGD and osteoporosis. The RNA immunoprecipitation sequencing assay identified all of the RNAs that bind with IGF2BP2, and revealed SRF as a target of IGF2BP2. IGF2BP2 and SRF inhibition impaired MC3T3-E1 cell growth but promoted OGD. The mRNA stability analysis revealed that IGF2BP2 enhanced SRF mRNA stability against degradation. In summary, IGF2BP2 is a potential biomarker and therapeutic target for osteoporosis and OGD.
Assuntos
Osteogênese , Osteoporose , Proteínas de Ligação a RNA , Fator de Resposta Sérica , Humanos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Osteogênese/genética , Osteoporose/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Fator de Resposta Sérica/genética , Fator de Resposta Sérica/metabolismo , Animais , CamundongosRESUMO
Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) can mediate DNA methylation and histone modifications in the epigenetic regulation of gene expression, stem cell differentiation and tumorigenesis. Here, we analyzed the differentially expressed mRNAs (DEmRNAs) in osteogenesis differentiation of MSCs and osteosarcoma. We identified UHRF1 as the co-DEmRNA to regulate the osteogenesis differentiation of MSCs and osteosarcoma. Moreover, we determined that the functions and pathways of UHRF1 in osteosarcoma. This finding indicates that UHRF1 is closely associated with metastasis and recurrence in osteosarcoma. Based on this finding, we derived a risk signature using UHRF1. In conclusion, UHRF1 is a crucial role in the malignant progression of osteosarcoma and are potentially useful for osteosarcoma progression treatment strategy development.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular/genética , Metilação de DNA , Epigênese Genética , Humanos , Osteogênese/genética , Osteossarcoma/genética , Prognóstico , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Lung adenocarcinoma (LUAD), the most common type of lung cancer associated with poor prognosis, has become a major health problem. IGF2BPs are types of N6-methyladenosine reader proteins, comprising IGF2BP1, IGF2BP2, and IGF2BP3, that promote LUAD progression. However, the expression profiles and prognostic value of IGF2BPs in LUAD remain unclear. OBJECTIVE: This study aimed to analyze the expression profiles and prognostic significance of the IGF2BP family in lung adenocarcinoma. METHODS: In this study, we included tissue data of LUAD patients and normal or para-carcinoma from the TCGA database and the GTEx project. Using survival analysis, Kaplan-Meier curves, and Cox proportional hazards model, we analyzed the expression profiles and prognostic significance of the IGF2BP family. RESULTS: Patients with high expression levels of IGF2BPs showed a significant association with poor overall survival (p < 0.05). Moreover, the somatic mutation rates of IGF2BP1, IGF2BP2, and IGF2BP3 were determined as 2.65, 1.59, and 1.76%, respectively, by investigating the genetic mutation. In addition, there were significant associations between TMB and IGF2BP family expression profiles, which positively correlated with the expression of PD-1 (p < 0.05). Cox proportional hazard model for LUAD showed the risk score for IGF2BP1, p-TNM stage, and so forth, all independent prognostic indicators for LUAD patients. Finally, the co-expression genes were obtained to build a PPI network and analyze the hub genes of the IGF2BP family. CONCLUSION: Our study provides further insights into the role of the IGF2BP family in LUAD and identifies 10 genes that may be associated with IGF2BPs in LUAD patients.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Ligação a RNA , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Família Multigênica , Prognóstico , Proteínas de Ligação a RNA/genéticaRESUMO
BACKGROUND: Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. RESULTS: A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. CONCLUSION: The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.
Assuntos
Diferenciação Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica , Osteogênese/genética , Osteoporose/genética , RNA Longo não Codificante/genética , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Humanos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteócitos/citologia , Osteócitos/metabolismo , Transdução de Sinais/genéticaRESUMO
Long noncoding RNAs (lncRNAs), as an important type of RNA encoded in the human transcriptome, have shown to regulate different genomic processes in human cells, altering cell type and function. These factors are associated with carcinogenesis, cancer metastasis, bone diseases, and immune system diseases, among other pathologies. Although many lncRNAs are involved in various diseases, the molecular mechanisms through which lncRNAs contribute to regulation of disease are still unclear. The lncRNA growth arrest-specific 5 (GAS5) is a key player that we initially found to be associated with regulating cell growth, differentiation, and development. Further work has shown that GAS5 is involved in the occurrence and prognosis of bone diseases, such as osteoporosis, osteosarcoma, and postosteoporotic fracture. In this review, we discuss recent progress on the roles of GAS5 in bone diseases to establish novel targets for the treatment of bone diseases.
