Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.

UNASSIGNED: Computed tomography (CT) and magnetic resonance imaging (MRI) of the spine are fundamental non-invasive tools to investigate the status of the bone and soft tissue in vivo. A novel and promising approach is to investigate the quality and quantity of paraspinal muscles even beyond the clinical question. The aim of the present review is to summarize current evidence on CT and MRI about the relationship between paraspinal muscular status and bone health in osteoporosis (OP) and fracture risk.
UNASSIGNED: Literature research was carried out on September 2023 using PubMed, Scopus, and Cochrane databases.
UNASSIGNED: Research investigating the intricate interplay between musculature and bone health reveals that degenerating paraspinal muscles, characterized by shrinking and fatty infiltration, are associated with lower bone mineral density (BMD) and the development of OP. Additionally, research indicates that weaker paraspinal muscles are linked to a higher risk of fractures, including those at the spine.
UNASSIGNED: The findings suggest that paraspinal muscle health may be a significant factor in identifying individuals at risk for OP and fractures. Further investigation is needed to explore the potential of paraspinal muscles in preventing these conditions.

BACKGROUND: Osteoporosis (OP), the \"silent epidemic\" of our century, poses a significant challenge to public health, predominantly affecting postmenopausal women and the elderly. It evolves from mild symptoms to pronounced severity, stabilizing eventually. Unique among OP\'s characteristics is the altered metabolic profile of affected cells, particularly in pyrimidine metabolism (PyM), a crucial pathway for nucleotide turnover and pyrimidine decomposition. While metabolic adaptation is acknowledged as a therapeutic target in various diseases, the specific role of PyM genes (PyMGs) in OP\'s molecular response remains to be clarified.
METHODS: In pursuit of elucidating and authenticating PyMGs relevant to OP, we embarked on a comprehensive bioinformatics exploration. This entailed the integration of Weighted Gene Co-expression Network Analysis (WGCNA) with a curated list of 37 candidate PyMGs, followed by the examination of their biological functions and pathways via Gene Set Variation Analysis (GSVA). The Least Absolute Shrinkage and Selection Operator (LASSO) technique was harnessed to identify crucial hub genes. We evaluated the diagnostic prowess of five PyMGs in OP detection and explored their correlation with OP\'s clinical traits, further validating their expression profiles through independent datasets (GSE2208, GSE7158, GSE56815, and GSE35956).
RESULTS: Our analytical rigor unveiled five PyMGs-IGKC, TMEM187, RPS11, IGLL3P, and GOLGA8N-with significant ties to OP. A deeper dive into their biological functions highlighted their roles in estrogen response modulation, cytosolic calcium ion concentration regulation, and GABAergic synaptic transmission. Remarkably, these PyMGs emerged as potent diagnostic biomarkers for OP, distinguishing affected individuals with substantial accuracy.
CONCLUSIONS: This investigation brings to light five PyMGs intricately associated with OP, heralding new avenues for biomarker discovery and providing insights into its pathophysiological underpinnings. These findings not only deepen our comprehension of OP\'s complexity but also herald the advent of more refined diagnostic and therapeutic modalities.

BACKGROUND: Osteoporosis (OP) stands as a prevalent bone ailment affecting the elderly, globally. The identification of reliable diagnostic markers crucially aids OP clinical management.
METHODS: Utilizing the GEO database (GSE35959), we acquired expression profiles for OP and normal samples. Differential expression genes (DEGs) and hub genes were pinpointed through STRING, GEO2R, and Cytoscape. The competing endogenous RNA (ceRNA) network was constructed using miRTarBase, miRDB, and MiRcode databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via DAVID. Validation involved clinical OP samples from the Pakistani population, with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assessing hub gene expression.
RESULTS: A total of 2124 differentially expressed genes (DEGs) were identified between OP and normal samples in GSE35959. The selected hub genes among these DEGs were Splicing Factor 3a Subunit 1 (SF3A1), Ataxin 2 Like (ATXN2L), Heat Shock Protein 90 Beta Family Member 1 (HSP90B1), Cluster of Differentiation 74 (CD74), DExH-Box Helicase 29 (DHX29), ALG5 Dolichyl-Phosphate Beta-Glucosyltransferase (ALG5), NudC Domain Containing 2 (NUDCD2), and Ras-related protein Rab-2A (RAB2A). Expression validation of these genes on the Pakistani OP patients revealed significant up-regulation of SF3A1, ATXN2L, and CD74 and significant (P < 0.05) down-regulation of HSP90B1, DHX29, ALG5, NUDCD2, and RAB2A in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these hub genes displayed considerable diagnostic accuracy for detecting OP. The ceRNA network analysis of the hub genes revealed some important hub genes\' regulatory miRNAs and lncRNAs. Via KEGG analysis, hub genes were found to be enriched in N-Glycan biosynthesis, Thyroid hormone synthesis, IL-17 signaling pathway, Prostate cancer, AMPK signaling pathway, Spliceosome, Estrogen signaling pathway, and Fluid shear stress and atherosclerosis, etc., pathways.
CONCLUSIONS: The identified eight hub genes in the present study could reliably distinguish OP patients from normal individuals, which may provide novel insight into the diagnostic research of OP.

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the β-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

Osteoporosis (OP) and ulcerative colitis (UC), prevalent immune diseases, exert a substantial socioeconomic impact globally. This study identifies biomarkers for these diseases, paving the way for in-depth research. Initially, the Gene Expression Omnibus (GEO) database was employed to analyze datasets GSE35958 and GSE87466. This analysis aimed to pinpoint co-expression differential genes (DEGs) between OP and UC. Subsequently, the Metascape database facilitated the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these DEGs\' co-expression. For network construction and visualization, the STRING11.5 database along with Cytoscape 3.7.2 (Cytoscape Team, USA) were utilized to create a protein-protein interaction (PPI) network. Moreover, Cytoscape\'s cytoHubba plugin was instrumental in identifying the central genes, known as hub genes. In the datasets GSE35958 and GSE87466, 156 co-expressed DEGs were discovered. The PPI network, constructed using STRING11.5 and Cytoscape 3.7.2, comprises 96 nodes and 222 connections. Notably, seven hub genes were identified, namely COL6A1, COL6A2, BGN, NID1, PLAU, TGFB1, and PLAUR. These DEGs were predominantly enriched in pathways such as extracellular matrix organization and collagen-containing extracellular matrix, as per GO analysis. For diagnostic model construction and hub gene validation, datasets GSE56815 and GSE107499 from the GEO database were employed. The top five hub genes were validated. In conclusion, the hub genes identified in this study played a significant role in the early diagnosis, prevention, and treatment of OP and UC. Furthermore, they provide fresh insights into the underlying mechanisms of these diseases\' development and progression.

BACKGROUND: Osteoporosis (OP), often referred to as the \"silent disease of the twenty-first century,\" poses a significant public health concern due to its severity, chronic nature, and progressive course, predominantly affecting postmenopausal women and elderly individuals. The pathogenesis and progression of this disease have been associated with dysregulation in tumor metabolic pathways. Notably, the metabolic utilization of glutamine has emerged as a critical player in cancer biology. While metabolic reprogramming has been extensively studied in various malignancies and linked to clinical outcomes, its comprehensive investigation within the context of OP remains lacking.
METHODS: This study aimed to identify and validate potential glutamine metabolism genes (GlnMgs) associated with OP through comprehensive bioinformatics analysis. The identification of GlnMgs was achieved by integrating the weighted gene co-expression network analysis and a set of 28 candidate GlnMgs. Subsequently, the putative biological functions and pathways associated with GlnMgs were elucidated using gene set variation analysis. The LASSO method was employed to identify key hub genes, and the diagnostic efficacy of five selected GlnMgs in OP detection was assessed. Additionally, the relationship between hub GlnMgs and clinical characteristics was investigated. Finally, the expression levels of the five GlnMgs were validated using independent datasets (GSE2208, GSE7158, GSE56815, and GSE35956).
RESULTS: Five GlnMgs, namely IGKC, TMEM187, RPS11, IGLL3P, and GOLGA8N, were identified in this study. To gain insights into their biological functions, particular emphasis was placed on synaptic transmission GABAergic, inward rectifier potassium channel activity, and the cytoplasmic side of the lysosomal membrane. Furthermore, the diagnostic potential of these five GlnMgs in distinguishing individuals with OP yielded promising results, indicating their efficacy as discriminative markers for OP.
CONCLUSIONS: This study discovered five GlnMgs that are linked to OP. They shed light on potential new biomarkers for OP and tracking its progression.

The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD+-dependent deacylase, SIRT6 (SIR2-like protein 6) is widely expressed on various kinds of bone cells, such as chondrocytes, osteoblasts, osteoclasts. The aberration of SIRT6 impairs gene expression (e.g., NF-κB and Wnt target genes) and cellular functions (e.g., DNA repair, glucose and lipid metabolism, telomeric maintenance), which disturbs the dynamic balance and ultimately leads to several bone-related diseases. In this review, we summarize the critical roles of SIRT6 in the onset and progression of bone-related diseases including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, as well as the relevant signaling pathways. In addition, we discuss the advances in the development of SIRT6 activators and elucidate their pharmacological profiles, which may provide novel treatment strategies for these skeletal diseases.

Degenerative orthopedic diseases, as a global public health problem, have made serious negative impact on patients\' quality of life and socio-economic burden. Traditional treatments, including chemical drugs and surgical treatments, have obvious side effects and unsatisfactory efficacy. Therefore, biological therapy has become the focus of researches on degenerative orthopedic diseases. Extracellular vesicles (EVs), with superior properties of immunoregulatory, growth support, and drug delivery capabilities, have emerged as a new cell-free strategy for the treatment of many diseases, including degenerative orthopedic diseases. An increasing number of studies have shown that EVs can be engineered through cargo loading, surface modification, and chemical synthesis to improve efficiency, specificity, and safety. Herein, a comprehensive overview of recent advances in engineering strategies and applications of engineered EVs as well as related researches in degenerative orthopedic diseases, including osteoarthritis (OA), osteoporosis (OP), intervertebral disc degeneration (IDD) and osteonecrosis of the femoral head (ONFH), is provided. In addition, we analyze the potential and challenges of applying engineered EVs to clinical practice.