Fragility fractures have been a cause for concern because of their high incidence. For the prevention and treatment of osteoporotic fractures, it is important to understand how to promote bone formation and increase bone mass. This study investigated miR-296-3p expression and function in fragility fracture. The study enrolled 98 patients with hip fractures, 90 patients with wrist fractures and 35 healthy controls. RT-qPCR was used to detect the miR-296-3p level changes before and after surgery in fracture patients and during the differentiation of human bone mesenchymal stem cells (BMSCs). The starBase bioinformatics database was used for prediction of the miR-296-3p target gene, and dual luciferase report was used for verification of the target relationship. Our results demonstrated that miR-296-3p levels are up-regulated in fracture patients, while they gradually decrease during human BMSC differentiation. The up-regulation of miR-296-3p inhibited the proliferation and differentiation ability of human BMSCs, while inhibition of its expression had the opposite effects. miR-296-3p negatively regulates osteogenic differentiation, and over-expression of inhibitor of β-catenin and TCF (ICAT) could counteract the negative regulatory effect. miR-296-3p targets ICAT and affects the expression of key proteins in the Wnt/β-catenin signalling pathway. In conclusion, miR-296-3p can regulate the division and differentiation of osteoblasts by affecting the expression of ICAT and participate in fracture healing.

• Keywords
• BMSCs, ICAT, fragility fractures, miR-296-3p,
• MeSH
• Cell Differentiation * genetics   MeSH
• Fracture Healing * genetics   physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesenchymal Stem Cells metabolism   cytology   MeSH
• MicroRNAs * metabolism   genetics   MeSH
• Osteogenesis * genetics   MeSH
• Cell Proliferation genetics   MeSH
• Aged MeSH
• Wnt Signaling Pathway genetics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• MicroRNAs * MeSH
• MIRN296 microRNA, human MeSH Browser

This study investigates the impact of hydroxyapatite (HA) nanoparticles (NPs) on the cellular responses of poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds in bone tissue engineering applications. Three types of PLCL scaffolds were fabricated, varying in HANPs content. Saos-2 osteoblast-like cells (OBs) and THP-1-derived osteoclast-like cells (OCs) were co-cultured on the scaffolds, and cell proliferation was assessed using the MTS assay. The amount of double-stranded DNA (dsDNA) was quantified to evaluate cell proliferation. Expression levels of OBs and OCs markers were analyzed via quantitative polymerase chain reaction (qPCR) and the production of Collagen type I was visualized using confocal microscopy. Additionally, enzymatic activity of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP or ACP5) was measured to assess OB and OC function, respectively. Interestingly, despite the scaffold's structured character supporting the growth of the Saos-2 OBs and THP-1-derived OCs coculture, the incorporation of HANPs did not significantly enhance cellular responses compared to scaffolds without HANPs, except for collagen type I production. These findings suggest the need for further investigation into the potential benefits of HANPs in bone tissue engineering applications. Nevertheless, our study contributes valuable insights into optimizing biomaterial design for bone tissue regeneration, with implications for drug screening and material testing protocols.

• Keywords
• PLCL, bone regeneration, hydroxyapatite, osteoblasts, osteoclasts, scaffold, tissue engineering,
• MeSH
• Cell Line MeSH
• Durapatite * chemistry   MeSH
• Coculture Techniques MeSH
• Humans MeSH
• Nanoparticles * chemistry   MeSH
• Nanofibers * chemistry   MeSH
• Osteoblasts cytology   metabolism   drug effects   MeSH
• Osteogenesis MeSH
• Osteoclasts cytology   metabolism   drug effects   MeSH
• Polyesters * chemistry   MeSH
• Cell Proliferation drug effects   MeSH
• Bone Regeneration * drug effects   MeSH
• THP-1 Cells MeSH
• Tissue Engineering methods   MeSH
• Tissue Scaffolds chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Durapatite * MeSH
• poly(lactic acid-co-epsilon-caprolactone) MeSH Browser
• Polyesters * MeSH

Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed via Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.

• Keywords
• Extracellular vesicles, Human granulosa cells, Osteodifferentiation,
• MeSH
• Cell Differentiation * MeSH
• Extracellular Vesicles * ultrastructure   metabolism   MeSH
• Follicular Fluid * cytology   metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mesenchymal Stem Cells * cytology   metabolism   MeSH
• Osteoblasts cytology   metabolism   MeSH
• Osteogenesis * MeSH
• Flow Cytometry MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The etiology of bone loss in celiac disease (CeD) remains a clinical challenge, with uncertainties present such as the extent of involvement of malabsorption and inflammation-induced osteoresorption processes in development of osteopenia/osteoporosis (OPN/OP), or reasons for failure to achieve healthy bone mass (BMD) even after long-term gluten-free diet (GFD) treatment. This observational prospective study explores the in vitro osteoclastogenic potential of peripheral blood precursors originating from adult active (newly diagnosed and untreated) celiac disease patients (aCeD) and describes the longitudinal changes in osteoclastogenesis after long-term adherence to GFD. To find connections between in vitro observations and in vivo bone metabolism changes, serum levels of 25(OH)D3, PTH, bCTX, PINP, CRP, IL-6, RANKL and OPG were measured before and after GFD and levels of these markers were correlated with the rate of osteoclastogenesis in vitro. OPG and IL-6 showed associations with BMD and/or presence of OPN/OP. Patients after GFD (CeD-GFD) exhibited improved BMD and increased serum 25(OH)D3 levels, alongside reduced bCTX and PINP levels. Compared to healthy donors, aCeD osteoclast genesis in vitro was higher and, surprisingly, remained elevated even in CeD-GFD patients. Negative correlation was found between osteoclastogenesis rate and serum OPG in aCeD, while osteoclastogenesis rate positively correlated with PTH in CeD-GFD. These results highlight OPG as marker for risk of OPN/OP in CeD and suggest that improvement of BMD after GFD is a result of uncoupling between bone metabolism and osteoresorptive action of osteoclasts after GFD.

• Keywords
• Bone metabolism, Celiac disease, Gluten-free diet, Osteoclastogenesis, Osteoporosis,
• MeSH
• Diet, Gluten-Free * MeSH
• Celiac Disease * diet therapy   complications   blood   physiopathology   MeSH
• Adult MeSH
• Interleukin-6 * blood   MeSH
• Bone and Bones * metabolism   MeSH
• Bone Density MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Osteogenesis * MeSH
• Osteoclasts metabolism   MeSH
• Osteoprotegerin * blood   MeSH
• Parathyroid Hormone blood   MeSH
• Prospective Studies MeSH
• Vitamin D * blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• IL6 protein, human MeSH Browser
• Interleukin-6 * MeSH
• Osteoprotegerin * MeSH
• Parathyroid Hormone MeSH
• TNFRSF11B protein, human MeSH Browser
• Vitamin D * MeSH

OBJECTIVE: Insulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602K, on human mesenchymal stem cells (MSCs). METHODS: We developed 13C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). In BM-MSCs, MSDC-0602K promoted osteoblastic differentiation and suppressed adipogenesis. This effect was clearly distinct from that of the earlier drugs and that on AT-MSCs. RESULTS: Fluxomic data reveal unexpected differences between this drug's effect on MSCs and provide mechanistic insight into the pharmacologic inhibition of mitochondrial pyruvate carrier 1 (MPC). Our study demonstrates that MSDC-0602K retains the capacity to inhibit MPC, akin to rosiglitazone but unlike pioglitazone, enabling the utilization of alternative metabolic pathways. Notably, MSDC-0602K exhibits a limited lipogenic potential compared to both rosiglitazone and pioglitazone, each of which employs a distinct lipogenic strategy. CONCLUSIONS: These findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.

• Keywords
• Adipocyte, Bone marrow, Lipid flux analysis, Mitochondrial pyruvate carrier, Tracer metabolomics,
• MeSH
• Adipogenesis * drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Hypoglycemic Agents * pharmacology   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Metabolomics methods   MeSH
• Mesenchymal Stem Cells drug effects   metabolism   MeSH
• Osteogenesis * drug effects   MeSH
• Pioglitazone MeSH
• Rosiglitazone pharmacology   MeSH
• Thiazolidinediones * pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hypoglycemic Agents * MeSH
• Pioglitazone MeSH
• Rosiglitazone MeSH
• Thiazolidinediones * MeSH

INTRODUCTION: The primary aim of this study was to assess the amount and long-term stability of orthodontically created bone in patients with agenesis of maxillary lateral incisors after canine distalization. The secondary aim was to explore the impact of patient age on the process of alveolar bone resorption. METHODS: A group of patients with agenesis of the maxillary permanent lateral incisor was examined at 4 time points: the beginning of orthodontic treatment (T1, n = 80), the end of treatment (T2, n = 80), 2-5 years after treatment (T3, n = 79), and 12-15 years after treatment (T4, n = 32). The width of the edentulous alveolar bone was measured from study casts at the level of the bone ridge (point A) and 5 mm apically from the alveolar ridge (point B). Alveolar ridge height was also recorded using panoramic radiographs at all time points. Paired t tests, 2-sample t tests, Friedman test with Bonferroni correction, Spearman`s correlation, and linear regression tests were used to analyze the data. RESULTS: The alveolar ridge width was reduced by an average of 0.44 mm at point A and 0.47 mm at point B during the 12-15 years after treatment (T2-T4) and by 0.21 mm and 0.19 mm during the last 10 years (T3-T4). The alveolar ridge height was reduced by 0.59 mm between T2 and T4 and by 0.05 mm between T3 and T4. All reductions in ridge width and height were statistically significant (P <0.05). However, no significant correlation was observed between patient age and changes in alveolar bone parameters (P >0.05). CONCLUSIONS: Although the reductions in alveolar ridge dimensions were statistically significant, the orthodontically created bone after canine distalization remained stable 12-15 years after treatment in both the horizontal and vertical dimensions. Patient age did not significantly influence alveolar bone changes.

• MeSH
• Anodontia * therapy   MeSH
• Jaw, Edentulous * diagnostic imaging   MeSH
• Child MeSH
• Adult MeSH
• Humans MeSH
• Maxilla * pathology   diagnostic imaging   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Osteogenesis * physiology   MeSH
• Tooth Movement Techniques * methods   MeSH
• Alveolar Process * pathology   diagnostic imaging   MeSH
• Radiography, Panoramic MeSH
• Alveolar Bone Loss etiology   diagnostic imaging   MeSH
• Incisor * abnormalities   MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Treatment of gingival fibroblasts with PDL extracellular vesicles results in promotion of Wnt signalling pathway and osteogenic differentiation. PDL secretome shows selective wound healing and matrix remodelling which can have implications for future periodontal regenerative strategies.

• MeSH
• Cell Differentiation MeSH
• Extracellular Vesicles * physiology   MeSH
• Fibroblasts physiology   MeSH
• Gingiva cytology   MeSH
• Wound Healing physiology   MeSH
• Humans MeSH
• Osteogenesis physiology   MeSH
• Periodontal Ligament * cytology   physiology   MeSH
• Regeneration * physiology   MeSH
• Wnt Signaling Pathway physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

This study introduces the first fabrication of porous titanium/hydroxyapatite interpenetrating phase composites through an innovative processing method. The approach combines additive manufacturing of a customized titanium skeleton with the infiltration of an injectable hydroxyapatite foam, followed by in situ foam hardening at physiological temperature. This biomimetic process circumvents ceramic sintering and metal casting, effectively avoiding the formation of secondary phases that can impair mechanical performance. Hydroxyapatite foams, prepared using two foaming agents (polysorbate 80 and gelatine), significantly reinforce the titanium skeleton while preserving the microstructural characteristics essential for osteoinductive properties. The strengthening mechanisms rely on the conformation of the foams to the titanium surface, thereby enabling stable mechanical interlocking and effective interfacial stress transfer. This, combined with the mechanical constriction of phases, enhances damage tolerance and mechanical reliability of the interpenetrating phase composites. In addition, the interpenetrating phase composites feature a network of concave pores with an optimal size for bone repair, support human osteoblast proliferation, and exhibit mechanical properties compatible with bone, offering a promising solution for the efficient and personalized reconstruction of large bone defects. The results demonstrate a significant advancement in composite fabrication, integrating the benefits of additive manufacturing for bone repair with the osteogenic capacity of calcium phosphate ceramics.

• Keywords
• Bone repair, Ceramic matrix composite, Hydroxyapatite, Infiltration, Self-hardening, Titanium,
• MeSH
• Biocompatible Materials chemistry   pharmacology   MeSH
• Durapatite * chemistry   pharmacology   MeSH
• Bone and Bones drug effects   MeSH
• Bone Substitutes chemistry   pharmacology   MeSH
• Humans MeSH
• Osteoblasts drug effects   MeSH
• Osteogenesis drug effects   MeSH
• Porosity MeSH
• Cell Proliferation drug effects   MeSH
• Bone Regeneration drug effects   MeSH
• Materials Testing MeSH
• Titanium * chemistry   pharmacology   MeSH
• Tissue Scaffolds chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Durapatite * MeSH
• Bone Substitutes MeSH
• Titanium * MeSH

Craniofacial morphogenesis depends on complex cell fate decisions during the differentiation of post-migratory cranial neural crest cells. Molecular mechanisms of cell differentiation of mesenchymal cells to developing bones, cartilage, teeth, tongue, and other craniofacial tissues are still poorly understood. We performed single-cell transcriptomic analysis of craniofacial mesenchymal cells derived from cranial NCCs in mouse embryo. Using FACS sorting of Wnt1-Cre2 progeny, we carefully mapped the cell heterogeneity in the craniofacial region during the initial stages of cartilage and bone formation. Transcriptomic data and in vivo validations identified molecular determinants of major cell populations involved in the development of lower and upper jaw, teeth, tongue, dermis, or periocular mesenchyme. Single-cell transcriptomic analysis of Meis2-deficient mice revealed critical gene expression differences, including increased osteogenic and cell adhesion markers. This leads to affected mesenchymal cell differentiation and increased ossification, resulting in impaired bone, cartilage, and tongue formation.

• Keywords
• Bone, Cartilage, Craniofacial development, Meis2, Neural crest,
• MeSH
• Single-Cell Gene Expression Analysis MeSH
• Chondrogenesis genetics   MeSH
• Neural Crest cytology   embryology   MeSH
• Homeodomain Proteins genetics   MeSH
• Craniofacial Abnormalities * embryology   genetics   MeSH
• Mesenchymal Stem Cells metabolism   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Osteogenesis * genetics   MeSH
• RNA-Seq MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Homeodomain Proteins MeSH
• Mrg1 protein, mouse MeSH Browser

Bone nonunion delays fracture end repair and is associated with inflammation. Although bone nonunion can be effectively repaired in clinical practice, many cases of failure. Studies have confirmed that BMP-2 and nHA/PA66 repaired bone defects successfully. There are few studies on the effects of the combined application of BMP-2 and NHA/PA66 on bone nonunion osteogenesis and inflammation. We aimed to investigate the expression level of inflammation-related genes in patients with bone nonunion and the effect of BMP-2-infected mesenchymal stem cells combined with nHA/PA66 on the level of inflammation in femur nonunion rats. We searched for a gene expression profile related to bone nonunion inflammation (GSE93138) in the GEO public database. Bone marrow mesenchymal stem cells (MSCs) of SD rats were cultured and passed through. We infected the third generation of MSCs with lentivirus carrying BMP-2 and induced the infected MSCs to bone orientation. We detected the expression level of BMP-2 by RT-PCR and the cell viability and alkaline phosphatase (ALP) activity by CCK8 and then analyzed the cell adhesion ability. Finally, the levels of related inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and Erythrocyte Sedimentation Rate (ESR), were detected in nonunion rats. Our findings: The patients with nonunion had up-regulated expression of 26 differentially inflammatory genes. These genes are mainly enriched in innate immune response, extracellular region, calcium ion binding, Pantothenate and CoA biosynthesis pathways. The expression level of BMP-2 in the Lenti-BMP-2 group was higher (vs. empty lentivirus vector group: t=5.699; vs. uninfected group t=3.996). The cell activity of the MSCs + BMP-2 + nHA/PA66 group increased gradually. After being combined with nHA/PA66, MSCs transfected with BMP-2 spread all over the surface of nHA/PA66 and grew into the material pores. MSCs + BMP-2 + nHA/PA66 cells showed positive ALP staining, and the OD value of ALP was the highest. The levels of CRP, IL-6, TNF-alpha, and ESR in the MSCs + BMP-2 + nHA/PA66 group were lower than those in the MSCs and MSCs + nHA/PA66 group but higher than those in MSCs + BMP-2 group. The above comparisons were all P<0.05. The findings demonstrated that the expression level of inflammation-related genes increased in the patients with bone nonunion. The infection of MSCs by BMP-2 could promote the directed differentiation of MSCs into osteoblasts in the bone marrow of rats, enhance the cell adhesion ability and ALP activity, and reduce inflammation in rats with bone nonunion.

• MeSH
• Adult MeSH
• Femur metabolism   pathology   MeSH
• Femoral Fractures metabolism   genetics   MeSH
• Bone Morphogenetic Protein 2 * metabolism   genetics   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesenchymal Stem Cells * metabolism   MeSH
• Fractures, Ununited * genetics   metabolism   MeSH
• Osteogenesis MeSH
• Rats, Sprague-Dawley * MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Inflammation * metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Rats MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• BMP2 protein, human MeSH Browser
• Bone Morphogenetic Protein 2 * MeSH