Regulation Of Bone Metabolism Research Articles

Chroogomphus rutilus Regulates Bone Metabolism to Prevent Periodontal Bone Loss during Orthodontic Tooth Movement in Osteoporotic Rats

Chroogomphus rutilus Regulates Bone Metabolism to Prevent Periodontal Bone Loss during Orthodontic Tooth Movement in Osteoporotic Rats

Bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles for their targeting of the Wnt/Ca2+signaling pathway

One of the applications of nanotechnology is the synthesis of nanoparticles for targeted drug delivery and disease prevention. In the agricultural sector, nanotechnology holds great promise for improving animal health and productivity. The article discusses the advantages of «green» synthesis of selenium nanoparticles functionalized with the flavonoid quercetin and their potential in the prevention of bone diseases in broilers. Selenium is an important trace element that plays a crucial role in various physiological processes, including the regulation of bone metabolism. Its deficiency can lead to bone diseases such as osteoporosis and osteomalacia. On the other hand, quercetin, a naturally occurring plant compound, has been shown to have numerous health benefits, including anti-inflammatory, antioxidant, and anticancer properties. However, quercetin's bioavailability and stability are limited, making its therapeutic potential challenging to exploit. To overcome these limitations, we have developed bionanotechnological strategies for the synthesis of quercetin conjugates with selenium nanoparticles. This approach not only improves the stability and bioavailability of quercetin, but also allows for targeted delivery to specific tissues or cellular pathways. Functionalization of Selenium nanoparticles with the flavonoid quercetin promotes the effect of the nanoconjugate on the transcription factors Nrf2 and NF-kB, Wnt, key pathways that regulate the delicate balance of cellular redox status and responses to stress and inflammation, calcium and phosphorus metabolism. In this case, the target is the Wnt signaling pathway, a complex cascade of processes involved in bone metabolism. It has been found that the synthesized nanoselenium-quercetin bioconjugates modulate the Wnt signaling pathway in different ways. Firstly, they reduce the activity of the protein β-catenin, a key regulator of the Wnt signaling pathway, and help maintain a balance between bone formation and resorption, thus preventing bone disease. Secondly, these bioconjugates increase the activity of LRP6, a Wnt receptor protein, which further enhances the effectiveness of the signaling pathway. Finally, they affect the expression of genes activated by the Wnt signaling pathway, thus regulating the metabolism of calcium and phosphorus, important elements for bone health. The potential of these bionanotechnology strategies is enormous, especially in the agricultural sector. By preventing bone disease in broilers, disease prevention and poultry productivity can be significantly increased. The use of nanotechnology advances can serve as an environmentally friendly alternative to the use of antibiotics and other pharmaceuticals, contributing to the overall health and well-being of animals. Thus, the «green» synthesis of quercetin-functionalized selenium nanoparticles offers a promising solution for targeting the Wnt signaling pathway, regulating calcium and phosphorus metabolism, and preventing bone disease in broilers. This bionanotechnology approach not only improves the stability and bioavailability of quercetin, but also enhances its therapeutic potential. By harnessing the potential of nanotechnology in the agricultural sector, we can improve animal health, reduce disease and increase productivity, ultimately benefiting both animals and humans. Key words: bionanotechnology, «green» synthesis, Nrf2 factor, NFkB, Wnt, β-catenin, Selenium, Calcium, Phosphorus.

M6A demethylase FTO and osteoporosis: potential therapeutic interventions.

Osteoporosis is a common bone disease, characterized by a descent in bone mass due to the dysregulation of bone homeostasis. Although different studies have identified an association between osteoporosis and epigenetic alterations in osteogenic genes, the mechanisms of osteoporosis remain unclear. N6-methyladenosine (m6A) modification is a methylated adenosine nucleotide, which regulates the translocation, exporting, translation, and decay of RNA. FTO is the first identified m6A demethylase, which eliminates m6A modifications from RNAs. Variation in FTO disturbs m6A methylation in RNAs to regulate cell proliferation, differentiation, and apoptosis. Besides, FTO as an obesity-associated gene, also affects osteogenesis by regulating adipogenesis. Pharmacological inhibition of FTO markedly altered bone mass, bone mineral density and the distribution of adipose tissue. Small molecules which modulate FTO function are potentially novel remedies to the treatment of osteoporosis by adjusting the m6A levels. This article reviews the roles of m6A demethylase FTO in regulating bone metabolism and osteoporosis.

Роль вітаміну D у функціонуванні кісткових клітин

The review summarizes current literature data on the importance of vitamin D in bone cell function. An analytical search was conducted in the PubMed, MEDLINE, Embase, Scopus, and Web of Science databases from January 1, 2018, to June 01, 2023. The vitamin D metabolite 1α,25(OH)2D3 plays an important role in the regulation of mineral homeostasis and bone metabolism. It has catabolic and anabolic actions on osteoblasts, osteocytes and mature osteoclasts. In this review, we describe the direct and indirect effects of 1α,25(OH)2D3 on the function of mesenchymal stromal cells (MSCs), osteoblasts, osteocytes, and osteoclasts. Among the targets of vitamin D action in bone cells are vitamin D receptor (VDR) and cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). In osteoblasts and MSCs with CYP27B1 knockout, cell proliferation and differentiation are impaired, and in osteoclasts, the resorption activity and lifespan of these cells are increased. The role of VDR in bone cells was demonstrated in normal and VDR-knockout animal models. The relationship between 1α,25(OH)2D3 – VDR signal transduction by bone cells and calcium balance was analyzed. In osteocytes, as well as in osteoblasts, 1α,25(OH)2D3 regulates the expression of RANKL (receptor activator of nuclear factor kappa-B ligand)), and additionally in osteocytes regulates the expression of FGF-23. The interaction of many other factors in bone cells has been shown to control the biological activity of 1α,25(OH)2D3. Thus, the effect of vitamin D on bone cells is in the phase of active research and requires an in-depth study of the features of its autocrine and paracrine effects. Identification of the molecular links of the mechanism of action of 1α,25(OH)2D3 on bone metabolism will provide a fundamental basis for approaches to the treatment of vitamin D deficiency diseases.

Advances in the study of traditional Chinese medicine affecting bone metabolism through modulation of oxidative stress.

Bone metabolic homeostasis is dependent on coupled bone formation dominated by osteoblasts and bone resorption dominated by osteoclasts, which is a process of dynamic balance between bone formation and bone resorption. Notably, the formation of bone relies on the development of bone vasculature. Previous studies have shown that oxidative stress caused by disturbances in the antioxidant system of the whole organism is an important factor affecting bone metabolism. The increase in intracellular reactive oxygen species can lead to disturbances in bone metabolism, which can initiate multiple bone diseases, such as osteoporosis and osteoarthritis. Traditional Chinese medicine is considered to be an effective antioxidant. Cumulative evidence shows that the traditional Chinese medicine can alleviate oxidative stress-mediated bone metabolic disorders by modulating multiple signaling pathways, such as Nrf2/HO-1 signaling, PI3K/Akt signaling, Wnt/β-catenin signaling, NF-κB signaling, and MAPK signaling. In this paper, the potential mechanisms of traditional Chinese medicine to regulate bone me-tabolism through oxidative stress is summarized to provide direction and theoretical basis for future research related to the treatment of bone diseases with traditional Chinese medicine.

Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk

Identification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in mice. The quantity and bioactivity of Mu-EVs were tightly correlated with the function of skeletal muscle. Proteomic analysis revealed numerous proteins in Mu-EVs, some potentially regulating bone metabolism, especially glycolysis. Subsequent investigations indicated that Mu-EVs promoted the glycolysis of BMSCs by delivering lactate dehydrogenase A into these cells. In summary, these findings reveal that Mu-EVs play a vital role in BMSC metabolism regulation and bone formation stimulation, offering a promising approach for treating disuse osteoporosis.

Effects of low-level laser on the expression of interleukin-6, tumor necrosis factor‑α, osteoprotegerin, and receptor activator of nuclear factor-κB ligand in human periodontal ligament cells.

This study aims to determine the effects of low-level laser (LLL) on the expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) stimulated by high glucose; and identify the molecular mechanism of LLL therapy in the regulation of periodontal inflammation and bone remodeling during orthodontic treatment in diabetic patients. HPDLCs were cultured in vitro to simulate orthodontic after loading and irradiated with LLL therapy. The cultured cells were randomly divided into four groups: low glucose Dulbecco's modification of Eagle's medium (DMEM)+stress stimulation (group A), high glucose DMEM+stress stimulation (group B), hypoglycemic DMEM+LLL therapy+stress stimulation (group C), and hyperglycemic DMEM+LLL therapy+stress stimulation (group D). Groups C and D were further divided into C1 and D1 (energy density: 3.75 J/cm2) and C2 and D2 (energy density: 5.625 J/cm2). Cells in groups A, B, C, and D were irradiated by LLL before irradiation. At 0, 12, 24, 48, and 72 h, the supernatants of the cell cultures were extracted at regular intervals, and the protein expression levels of IL-6, TNF-α, OPG, and RANKL were detected by enzyme-linked immunosorbent assay. 1) The levels of IL-6 and TNF-α secreted by HPDLCs increased gradually with time under static pressure stimulation. After 12 h, the levels of IL-6 and TNF-α secreted by HPDLCs in group A were significantly higher than those in groups B, C1, and C2 (P<0.05), which in group B were significantly higher than those in groups D1, and D2 (P<0.01). 2) The OPG protein concentration showed an upward trend before 24 h and a downward trend thereafter. The RANKL protein concentration increased, whereas the OPG/RANKL ratio decreased with time. Significant differen-ces in OPG, RANKL, and OPG/RANKL ratio were found among group A and groups B, C1, C2 as well as group B and groups D1, D2 (P<0.05). 1) In the high glucose+stress stimulation environment, the concentrations of IL-6 and TNF-α secreted by HPDLCs increased with time, the expression of OPG decreased, the expression of RANKL increased, and the ratio of OPG/RANKL decreased. As such, high glucose environment can promote bone resorption. After LLL therapy, the levels of IL-6 and TNF-α decreased, indicating that LLL therapy could antagonize the increase in the levels of inflammatory factors induced by high glucose environment and upregulate the expression of OPG in human HPDLCs, downregulation of RANKL expression in HPDLCs resulted in the upregulation of the ratio of OPG/RANKL and reversed the imbalance of bone metabolism induced by high glucose levels. 2) The decrease in inflammatory factors and the regulation of bone metabolism in HPDLCs were enhanced with increasing laser energy density within 3.75-5.625 J/cm2. Hence, the ability of LLL therapy to modulate bone remodeling increases with increasing dose.

Hypoxia dissociates HDAC6/FOXO1 complex and aggregates them into nucleus to regulate autophagy and osteogenic differentiation.

This research aimed to elucidate the molecular mechanisms underlying the periodontitis-associated bone loss, with particular emphasis on the contributory role of hypoxic microenvironment in this process. Periodontitis generally causes alveolar bone loss and is often associated with a hypoxic microenvironment, which affects bone homeostasis. However, the regulating mechanism between hypoxia and jaw metabolism remains unclear. Hypoxia triggers autophagy, which is closely related to osteogenic differentiation, but how hypoxia-induced autophagy regulates bone metabolism is unknown. HDAC6 and FOXO1 are closely related to bone metabolism and autophagy, respectively, but whether they are related to hypoxia-induced bone loss and their internal mechanisms is still unclear. Established rat nasal obstruction model and hypoxia cell model. Immunohistochemistry was performed to detect the expression and localization of HDAC6 and FOXO1 proteins, analysis of autophagic flux and transmission electron microscopy was used to examine the autophagy level and observe the autophagosomes, co-immunoprecipitation and chromatin immunoprecipitation were preformed to investigate the interaction of HDAC6 and FOXO1. Hypoxia causes increased autophagy and reduced osteogenic differentiation in rat mandibles and BMSCs, and blocking autophagy can attenuate hypoxia-induced osteogenic differentiation decrease. Moreover, hypoxia dissociated the FOXO1-HDAC6 complex and accumulated them in the nucleus. Knocking down of FOXO1 or HDAC6 alleviated hypoxia-induced autophagy elevation or osteogenic differentiation reduction by binding to related genes, respectively. Hypoxia causes mandibular bone loss and autophagy elevation. Mechanically, hypoxia dissociates the FOXO1-HDAC6 complex and aggregates them in the nucleus, whereas HDAC6 decreases osteogenic differentiation and FOXO1 enhances autophagy to inhibit osteogenic differentiation.

DOES VITAMIN D REDUCE THE MORTALITY RATE OF PLASMODIUM INFECTION? : A SYSTEMATIC REVIEW

Background: Malaria is widespread in tropical and subtropical regions, causing more than 300 million acute illnesses and resulting in more than 600,000 deaths annually. Vitamin D (VD) is a fat-soluble vitamin that is synthesized in the skin after exposure to solar ultraviolet B radiation or provided in food. In addition to its traditionally recognized role in the regulation of bone metabolism and calcium-phosphorus homeostasis, VD is increasingly recognized to have prominent regulatory functions in both the innate and adaptive immune systems. The aim: This study aims to show that vitamin D reduce the mortality rate of plasmodium infection or not. Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: In the PubMed database, the results of our search brought up 411 articles, whereas the results of our search on SagePub brought up 49 articles. The results of the search conducted for the last year of 2013 yielded a total 362 articles for PubMed and 36 articles for SagePub. The result from title screening, a total 4 articles for PubMed and 16 articles for SagePub. In the end, we compiled a total of 10 papers. We included five research that met the criteria. Conclusion: Vitamin D affects the survival rate of individuals infected with Plasmodium. Although mouse models may not accurately reproduce the clinical picture and pathophysiology of malaria in humans, the studies conducted have been instrumental in providing information on how to design appropriate studies in humans.

Genetic polymorphisms of rs73620203 in the transforming growth interacting factor gene associated with rheumatoid arthritis in a Chinese population

ObjectiveTo explore the association of single nucleotide polymorphisms (SNPs) in the transforming growth interacting factor (TGIF) gene with bone metabolism markers and rheumatoid arthritis (RA) susceptibility. MethodsThree SNPs were genotyped in 155 RA patients and 168 healthy controls using high-resolution melting (HRM) analysis. The serum levels of osteocalcin, bone alkaline phosphatase (BALP), and β type I collagen-crosslinked C telopeptide (β-CTX) were detected using electrochemical luminescence in 108 patients randomly selected from the RA group. ResultsGenotype and allele frequency analysis showed that rs73620203 was associated with bone erosion in RA (P = 0.012 and P = 0.003, respectively), and individuals carrying the T allele for rs73620203 showed a decreased RA risk (OR = 0.59, 95% CI = 0.42–0.84; P = 0.003). In sex-specific analysis, the rs73620203 polymorphism was associated with susceptibility to RA in women (P = 0.022 and P = 0.006, respectively). In addition, RA patients with three genotypes at the rs73620203 locus showed significant differences in serum osteocalcin and BALP (P = 0.006 and P = 0.037, respectively). Haplotype analysis revealed that the haploid ATG and GCA frequencies were significantly lower in the RA group (P = 0.036, OR = 0.693; P = 0.002, OR = 0.189, respectively), while the haploid ACA frequency of the RA group was enhanced (P < 0.01, OR = 5.058). ConclusionOur study provides the first evidence that rs73620203 is associated with RA susceptibility and the relationship between TGIF gene SNPs and the regulation of bone metabolism in RA patients.

Additive manufacturing of degradable magnesium alloys and their application in orthopedic implants

ABSTRACT Recently, with the continuous research on magnesium alloy materials, the production and processing technology of magnesium alloys are continuously improved, bringing in their improved mechanical properties and corrosion resistance. Therefore, magnesium alloys have once again become one of the research hotspots of orthopedic degradable materials. Meanwhile, the biocompatibility and biosafety properties of magnesium alloys were considered. The magnesium ions generated after the magnesium alloy is degraded in the body, will participate in the human body's metabolism, regulate bone metabolism activities, and contribute to the synthesis of new bone. Some research studied that magnesium ions can regulate the metabolic function of the human body through multiple signaling pathways, and in vitro cells, and experiments have proved this point of view. Therefore, magnesium alloys are expected to become a promising material in orthopedic treatment, due to their good biocompatibility, degradability, and mechanical properties. In this review, we provide an overview of the degradable magnesium alloys and some key surface treatments and additive manufacturing of these materials to promote their application in orthopedic implants.

The influence of growth hormone deficiency on bone health and metabolisms.

Growth hormone (GH) is a key peptide hormone in the regulation of bone metabolism, through its systemic and paracrine action mediated directly as well as by insulin-like growth factor-1 (IGF-1). Growth hormone exerts pleiotropic effects leading to an increase in linear bone growth, accumulation of bone mineral content and preservation of peak bone mass. Furthermore, it influences protein, lipid, and carbohydrate metabolism.Growth hormone deficiency (GHD) causes a low bone turnover rate leading to reduced bone mineral density (BMD) and increased bone fragility. The results of GH insufficiency are the most pronounced among children as it negatively affects longitudinal bone growth, causing short stature and in adolescents, in whom it hinders the acquisition of peak bone mass. Most studies show that treatment with recombinant human growth hormone (rhGH) in GHD patients could improve BMD and decrease fracture risk. This review aims to summarize the pathophysiology, clinical picture and management of bone complications observed in GHD.

Electrochemical biosensor based on NAD(P)H-dependent quinone reductase for rapid and efficient detection of vitamin K3

Vitamin K refers to a group of vitamins that play an important role in blood coagulation and regulation of bone and vascular metabolism. However, vitamin K3 may give severe side effects in animal and humans when improperly added to food and feed due to its toxicity. Here, an electrochemical biosensor, based on the YaiB NADPH-dependent quinone reductase from Lactococcus lactis (YaiB), was developed to achieve rapid and redox probe-free detection of vitamin K3. First, the ability of the carbon electrode to distinguish between 1,4-benzoquinone and hydroquinone was demonstrated. Then, we engineered YaiB to work as a bioreceptor immobilized at the electrode and its sensitivity and specificity to reduce vitamin K3 were demonstrated. Finally, to demonstrate the practical potential of the biosensor, we tested it directly in spiked milk samples, achieving 15-minute quantification of the vitamin K3. The limit of detection was 0.87 µM and 4.1 µM in buffer and milk, respectively.

Lipoteichoic acid inhibits osteoclast differentiation and bone resorption via interruption of gelsolin-actin dissociation.

Bone resorption can be caused by excessive differentiation and/or activation of bone-resorbing osteoclasts. While microbe-associated molecular patterns can influence the differentiation and activation of bone cells, little is known about the role of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, in the regulation of bone metabolism. In this study, we investigated the effect of LTA on bone metabolism using wild-type Staphylococcus aureus and the LTA-deficient mutant strain. LTA-deficient S. aureus induced higher bone loss and osteoclast differentiation than wild-type S. aureus. LTA isolated from S. aureus (SaLTA) inhibited osteoclast differentiation from committed osteoclast precursors in the presence of various osteoclastogenic factors by downregulating the expression of NFATc1. Remarkably, SaLTA attenuated the osteoclast differentiation from committed osteoclast precursors of TLR2-/- or MyD88-/- mice and from the committed osteoclast precursors transfected with paired immunoglobulin-like receptor B-targeting siRNA. SaLTA directly interacted with gelsolin, interrupting the gelsolin-actin dissociation which is a critical process for osteoclastogenesis. Moreover, SaLTA suppressed the mRNA expression of dendritic cell-specific transmembrane protein, ATPase H+ transporting V0 subunit D2, and Integrin, which encode proteins involved in cell-cell fusion of osteoclasts. Notably, LTAs purified from probiotics, including Bacillus subtilis, Enterococcus faecalis, and Lactobacillus species, also suppressed Pam2CSK4- or RANKL-induced osteoclast differentiation. Taken together, these results suggest that LTAs have anti-resorptive activity through the inhibition of osteoclastogenesis by interfering with the gelsolin-actin dissociation and may be used as effective therapeutic agents for the prevention or treatment of inflammatory bone diseases.

E24 Does juvenile onset impact the serum levels of bone-forming biomarkers in adult patients with Spondyloarthritis?

Abstract Introduction The Wnt signalling pathway regulates bone metabolism. Dickkopf1 (DKK-1) and Sclerostin are potent inhibitors of this pathway, and their dysfunction would be responsible for bone formation phenomena in patients with spondyloarthritis (SpA). Osteoprotegerin (OPG), a potent inhibitor of osteoclasts, regulated by the Wnt pathway, has also been implicated in this bone ossification phenomenon. We aimed to assess the impact of juvenile-onset on the serum levels of DKK-1, sclerostin, and OPG in adult with spondyloarthritis. Methods It was a cross-sectional case control study including patients with SpA (meeting ASAS criteria). Data collected included sociodemographic and disease characteristics. Biomarker assays were performed using an ELISA technique. Results Among one hundred and nine included patients, seven patients had a juvenile onset of the disease (six males, one female). The mean age of disease onset was 12.8 ± 4.3 [5–16] years. The mean duration of SpA at inclusion was 15 ± 6 years [4 – 21]. Two (28.6%) patients had an axial form, and five (71.4%) had an axial and peripheral form. Three patients (42.9%) had entheseal involvement. The means of serum levels of DKK-1 and sclerostin in patients with juvenile-onset SpA and healthy controls were (132 ± 81 vs 122 ± 113; P = 0.439) and (27 ± 15 vs 39 ± 49; P = 0.985) respectively. The analysis did not show significant differences in serum levels of DKK-1 (P = 0.293), sclerostin (P = 0.428), and OPG (P = 0.504) between patients with SpA with juvenile onset and adult SpA. Conclusion In our study the juvenile onset of the disease did not correlate with the inhibitors of the Wnt signalling pathway and OPG in patients with SpA.

Interleukin-17A Promotes Proliferation and Osteogenic Differentiation of Human Ligamentum Flavum Cells Through Regulation of β-Catenin Signaling.

A basic experimental study. To elucidate the role and mechanism of interleukin (IL)-17A in thoracic ossification of the ligamentum flavum (TOLF). TOLF is characterized by the replacement of the thoracic ligamentum flavum with ossified tissue and is one of the leading causes of thoracic spinal stenosis. IL-17A is an important member of the IL-17 family that has received widespread attention for its key contributions to the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF. Cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine staining were performed to assess the proliferation of ligamentum flavum cells (LFCs). Alkaline phosphatase activity assay, Alizarin red staining, and protein level expression of osteogenic-related genes were used to evaluate the osteogenic differentiation potential of LFCs. The effect of IL-17A on the proliferation and osteogenic differentiation of LFCs was further assessed after silencing β-catenin by transfection with small interfering RNA. In addition, the possible source of IL-17A was further demonstrated by coculture assays of T helper 17 (Th17) cells with LFCs. Student t test was used for comparisons between groups, and the one-way analysis of variance, followed by the Tukey post hoc test, was used for comparison of more than two groups. IL-17A was elevated in TOLF tissue compared with normal ligamentum flavum. IL-17A stimulation promoted the proliferation and osteogenic differentiation of LFCs derived from patients with TOLF. We found that IL-17A promoted the proliferation and osteogenic differentiation of LFCs by regulating the β-catenin signaling. Coculture of Th17 cells with LFCs enhanced β-catenin signaling-mediated proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A. This is the first work we are aware of to highlight the importance of IL-17A in TOLF. IL-17A secreted by Th17 cells in the ligamentum flavum may be involved in the ossification of the microenvironment by regulating β-catenin signaling to promote the proliferation and osteogenic differentiation of LFCs.

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis.

Bone homeostasis is a dynamic equilibrium state of bone formation and absorption, ensuring skeletal development and repair. Bone immunity encompasses all aspects of the intersection between the skeletal and immune systems, including various signaling pathways, cytokines, and the crosstalk between immune cells and bone cells under both homeostatic and pathological conditions. Therefore, as key cell types in bone immunity, macrophages can polarize into classical pro-inflammatory M1 macrophages and alternative anti-inflammatory M2 macrophages under the influence of the body environment, participating in the regulation of bone metabolism and playing various roles in bone homeostasis. M1 macrophages can not only act as precursors of osteoclasts (OCs), differentiate into mature OCs, but also secrete pro-inflammatory cytokines to promote bone resorption; while M2 macrophages secrete osteogenic factors, stimulating the differentiation and mineralization of osteoblast precursors and mesenchymal stem cells (MSCs), and subsequently increase bone formation. Once the polarization of macrophages is imbalanced, the resulting immune dysregulation will cause inflammatory stimulation, and release a large amount of inflammatory factors affecting bone metabolism, leading to pathological conditions such as osteoporosis (OP), rheumatoid arthritis (RA), and steroid-induced femoral head necrosis (SANFH). In this review, we introduce the signaling pathways and related factors of macrophage polarization, as well as their relationships with immune factors, OB, OC, and MSC. We also discuss the roles of macrophage polarization and bone immunity in various diseases of bone homeostasis imbalance, as well as the factors regulating them, which may help to develop new methods for treating bone metabolic disorders.

Deletion of osteopontin in non-small cell lung cancer cells affects bone metabolism by regulating miR-34c/Notch1 axis: a clue to bone metastasis.

Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.

Low bone mineral density is found in low weight female youth with avoidant/restrictive food intake disorder and associated with higher PYY levels

BackgroundAvoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD.MethodsWe performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10–23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood.ResultsTotal body BMD Z-scores were significantly lower in ARFID than in HC (− 1.41 ± 0.28 vs. − 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (β = -0.481, p = 0.032).ConclusionOur findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID.

Decreased Synovial Fluid Ghrelin Level Is Associated With Acute Cartilage Injury in Patients With Anterior Cruciate Ligament Tear.

Ghrelin, an amino acid hormone secreted primarily from the stomach, can regulate bone metabolism, regulate inflammation via suppressing proinflammatory cytokines, and suppress expression of matrix metalloproteinases (MMPs). To measure synovial fluid levels of ghrelin in young patients with anterior cruciate ligament (ACL) tear to assess the role of ghrelin as a potential biomarker for cartilage injury. Controlled laboratory study. This study included 120 patients who underwent ACL reconstructionbetween January 1, 2016, and May 31, 2021. We categorized 60 patients with acute cartilage injury (International Cartilage Regeneration & Joint Preservation Society grade 2 or 3) as the acute group and 60 patients with no acute cartilage injury as the nonacute group, with the healthy contralateral knee of each patient acting as the control group (n = 120). Synovial fluid samples were collected from the knees in the operating room before ACL reconstruction. We assessed the inflammatory biomarkers interleukin (IL)-6, MMP-1, MMP-9, and MMP-13, as well as serum ghrelin level and Mankin score, and results were compared between the 3 study groups with the Mann-Whitney U test. Lower serum ghrelin levels in the synovial fluid were found in the acute group compared with the nonacute group and healthy controls (232.4 vs 434.4 vs 421.5 pg/mL, respectively; P < .001). Ghrelin level in the synovial fluid was significantly and positively correlated with IL-6 (r = 0.4223; P < .0001), MMP-13 (r = 0.3402; P < .0001), and Mankin score (r = 0.1453; P = .0244). In patients with ACL injury, ghrelin synovial fluid was significantly differently expressed in patients with cartilage injury and no cartilage injury. Ghrelin synovial fluid has the potential to be a biomarker to predict acute cartilage injury in patients with ACL injury.