• 3D bioprinted scaffold
• Articular cartilage repair
• Gene therapy
• Gene-activated matrix
• Hydrogel

• bioreactor technology
• cartilage tissue engineering
• chondrocytes
• extracellular matrix
• regenerative medicine
• scaffold design
• space microgravity
• three-dimensional tissue growth

• Cancer cachexia
• adipose tissue transdifferentiation
• cancer
• exosome
• extracellular vesicles
• metabolism

• Adipogenic differentiation
• Epigenetic regulation
• Mesenchymal stem cell
• Noncoding RNA
• Signaling pathway

• 3D printing
• cell differentiation
• chondrogenesis
• human
• mesenchymal stem cells
• polycaprolactone
• sheep
• silica
• tetrahydrofuran

• cell biology
• developmental biology
• transcriptomics

• chondrogenic differentiation
• growth factors
• mesenchymal stem cells
• osteoarthritis
• peptides

• Degenerative joint diseases
• Intervertebral disc degeneration
• Osteoarthritis
• RNA-binding proteins

• Biomaterials
• Cartilage
• Nanocomposites
• Tissue engineering

• adipose-derived stem cells
• biomaterials
• modification
• stiffness
• topography

• Adipose Tissue/metabolism
• Adipocytes
• Mesenchymal Stem Cells/metabolism
• Cell Differentiation
• Biocompatible Materials/metabolism

The chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) has been used in the treatment and repair of cartilage defects; however, the in-depth regulatory mechanisms by which RNA modifications are involved in this process are still poorly understood. Here, we found that Sox9, a critical transcription factor that mediates chondrogenic differentiation, exhibited enhanced translation by ribosome sequencing in chondrogenic pellets, which was accompanied by increased 5-methylcytosine (m⁵C) and N6-methyladenosine (m⁶A) levels. Nsun4-mediated m⁵C and Mettl3-mediated m⁶A modifications were required for Sox9-regulated chondrogenic differentiation. Interestingly, we showed that in the 3’UTR of Sox9 mRNA, Nsun4 catalyzed the m⁵C modification and Mettl3 catalyzed the m⁶A modification. Furthermore, we found that Nsun4 and Mettl3 co-regulated the translational reprogramming of Sox9 via the formation of a complex. Surface plasmon resonance (SPR) assays showed that this complex was assembled along with the recruitment of Ythdf2 and eEF1α-1. Moreover, BMSCs overexpressing Mettl3 and Nsun4 can promote the repair of cartilage defects in vivo. Taken together, our study demonstrates that m⁵C and m⁶A co-regulate the translation of Sox9 during the chondrogenic differentiation of BMSCs, which provides a therapeutic target for clinical implications.

Nsun4-mediated m5C and Mettl3-mediated m6A are found to be required for Sox9-regulated chondrogenic differentiation, whereby Nsun4 and Mettl3 interact with each other and recruit Ythdf2 and eEF1a-1 to form a complex at the 3’UTR of Sox9.

The inability of cartilage to self-repair necessitates an effective therapeutic approach to restore damaged tissues. Extracellular vesicles (EVs) are attractive options because of their roles in cellular communication and tissue repair where they regulate the cellular processes of proliferation, differentiation, and recruitment. However, it is a challenge to determine the relevant cell sources for isolation of EVs with high chondrogenic potential. The current study aims to evaluate the chondrogenic potential of EVs derived from chondrocytes (Cho-EV) and mesenchymal stem cells (MSC-EV). The EVs were separately isolated from conditioned media of both rabbit bone marrow MSCs and chondrocyte cultures. The isolated vesicles were assessed in terms of size, morphology, and surface marker expression. The chondrogenic potential of MSCs in the presence of different concentrations of EVs (50, 100, and 150 μg/ml) was evaluated during 21 days, and chondrogenic surface marker expressions were checked by qRT-PCR and histologic assays. The extracted vesicles had a spherical morphology and a size of 44.25 ± 8.89 nm for Cho-EVs and 112.1 ± 10.10 nm for MSC-EVs. Both groups expressed the EV-specific surface markers CD9 and CD81. Higher expression of chondrogenic specified markers, especially collagen type II (COL II), and secretion of glycosaminoglycans (GAGs) and proteoglycans were observed in MSCs treated with 50 and 100 μg/ml MSC-EVs compared to the Cho-EVs. The results from the use of EVs, particularly MSC-EVs, with high chondrogenic ability will provide a basis for developing therapeutic agents for cartilage repair.

To investigate the presence of connective tissue progenitor cells (CTPs) in the trochanteric bursa harvested over the gluteus medius muscle belly and tendon during open hip procedures.

Trochanteric bursa samples from nine patients (63.1 ± 8.6 years) undergoing total hip arthroplasty for primary osteoarthritis were obtained from 2 sites: over the gluteus medius tendon at the greater trochanter and over the muscle belly. Bursal tissue was digested with collagenase and grown in culture. The nucleated cell count, cellular concentration, cellular proliferation, fluorescence-activated cell sorting (FACS) analysis, and differentiation using immunostaining and quantitative polymerase chain reaction (PCR) were used to determine and quantify the presence of CTPs.

Bursa-derived CTPs were identified in all harvested samples. At t = 0, there was no difference in nucleated cell count over muscle and tendon (1.69 ± 1.26 × 10⁸ and 1.41 ± 1.12 × 10⁸ cells/g, respectively; P = .162). Similarly, the cellular concentration at 3 weeks was not significantly different between bursa harvested over muscle and tendon (6.61 ± 5.14 × 10⁶ and 5.58 ± 4.70 × 10⁶ cells/g, respectively; P = .532). High cellular proliferation was identified for both bursal tissue overlying muscle and tendon (2.28 ± .95 and 1.66 ± 1.05, respectively; P = .194). FACS analysis revealed high positivity rates (>95%) of CTP-specific surface epitopes (CD105, CD90, and CD73) and low positivity rates (<1.3%) of negative markers (CD45, CD31). Osteogenic, adipogenic, and chondrogenic differentiation potential was demonstrated with immunostaining and quantitative PCR for gene expression.

Connective tissue progenitor cells are found in the trochanteric bursa overlying the muscle and tendon of the hip abductors.

During open hip procedures, the trochanteric bursa is often partially excised to identify muscular boundaries and tissue planes for surgical exposure. The function of the trochanteric bursa remains largely unknown. However, this tissue is a source of connective tissue progenitor cells, which may be important in the healing response of surgically repaired abductor tendons.

• Cytology treatment
• MSCs
• Meniscus injury

Osteoarthritis (OA), the most common type of arthritis, causes pain in joints and disability. Due to the absence of ideal effective medication, stem cell transplantation emerges as a new hope for OA therapy. This study is aimed at evaluating the capability of human umbilical cord mesenchymal stromal cells (HUCMSCs) mixed with hyaluronan (HA) to treat osteoarthritis in a rabbit model. Differentiation capability of HUCMSCs, magnetic resonance image examination, and immunohistochemistry of the cartilage after transplantation of HUCMSCs mixed with HA in a rabbit OA model were explored. HUCMSCs exhibited typical mesenchymal stromal cell (MSC) characteristics, including spindle-shaped morphology, surface marker expressions (positive for human leukocyte antigen- (HLA-) ABC, CD44, CD73, CD90, and CD105; negative for HLA-DR, CD34, and CD45), and trilineage differentiation (chondrogenesis, adipogenesis, and osteogenesis). The gene expression of SOX9, type II collagen, and aggrecan in the HUCMSC-derived chondrocytes mixed with HA was increased after in vitro chondrogenesis compared with HUCMSCs. A gross and histological significant improvement in hyaline cartilage destruction after HUCMSCs mixed with HA was noted in the animal model compared to the OA knees. The International Cartilage Repair Society histological score and Safranin O staining were significantly higher for the treated knees than the control knees (p < 0.05). Moreover, the expression of MMP13 was significantly decreased in the treated knees than in the OA knees. In conclusion, HUCMSCs mixed with HA in vitro and in vivo might attenuate the cartilage destruction in osteoarthritis. Our study provided evidence for future clinical trials.

Dental pulp stem cells (DPSCs) are candidate seed cells for bone tissue engineering, but the molecular regulation of osteogenic differentiation in DPSCs is not fully understood. Long non-coding RNAs (lncRNAs) are important regulators of gene expression, and whether they play roles in osteogenic differentiation of DPSCs requires more study.

DPSCs were isolated and cultured. The mRNA and lncRNA expression profiles were compared through microarray assay between osteo-differentiated DPSCs and non-differentiated DPSCs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene ontology (GO) analyses, and the mRNA-lncRNA co-expression analyses were performed for functional annotation of differentially expressed RNAs. Small interfering RNA (siRNA) was used to interfere the expression of lncRNA ENST00000533992 (also named smooth muscle-induced lncRNA or SMILR), a candidate regulator, then the osteogenic differentiation potential of DPSCs was analyzed.

DPSCs were isolated and cultured successfully. The expression of 273 mRNAs and 184 lncRNAs changed significantly in DPSCs after osteogenic induction. KEGG analyses and GO analyses showed that the differentially expressed RNAs were enriched in several pathways and biological processes. The mRNA-lncRNA co-expression network was constructed to reveal the potential relationships between mRNAs and lncRNAs. The osteogenic differentiation potential of DPSCs decreased when SMILR was interfered.

The present study provides clues for seeking for lncRNAs that participate in the regulation of osteogenic differentiation in DPSCs. LncRNA SMILR could play a role in regulating osteogenic differentiation of DPSCs.

• Chondrocyte maturation
• Dominant-negative protein
• Ebf
• Limb bud
• Short bone

• Animals
• Chick Embryo
• Chondrogenesis
• Gene Expression Regulation, Developmental
• Limb Buds/growth & development
• Limb Buds/metabolism
• Phenotype
• Trans-Activators/genetics
• Trans-Activators/metabolism

• BM-MSCs
• Wnt5a
• differentiation
• toll-like receptor 4

• Demineralized bone matrix
• cartilage tissue engineering
• chondrogenic differentiation
• injectability of scaffold
• mechanical properties
• polyvinyl alcohol

• Animals
• Biocompatible Materials/chemistry
• Biocompatible Materials/pharmacology
• Bone Matrix/chemistry
• Cartilage, Articular/pathology
• Cell Differentiation/drug effects
• Cell Proliferation/drug effects
• Cells, Cultured
• Chondrogenesis/drug effects
• Collagen Type II/metabolism
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/metabolism
• Models, Animal
• Polyvinyl Alcohol/chemistry
• Prostheses and Implants
• Rabbits
• SOXB1 Transcription Factors/metabolism
• Tissue Engineering
• Tissue Scaffolds
• Up-Regulation/drug effects

• Chondrogenesis differentiation
• Dynamic cell culture
• Polydimethylsiloxane
• Rat adipose stem cell
• Surface modification
• Transforming growth factor β1

This study identified key genes in gastric cancer (GC) based on the mRNA microarray GSE19826 from the Gene Expression Omnibus (GEO) database and preliminarily explored the relationships among the key genes.

Differentially expressed genes (DEGs) were obtained using the GEO2R tool. The functions and pathway enrichment of the DEGs were analyzed using the Enrichr database. Protein–protein interactions (PPIs) were established by STRING. A lentiviral vector was constructed to silence RUNX2 expression in MGC-803 cells. The expression levels of RUNX2 and FN1 were measured. The influences of RUNX2 and FN1 on overall survival (OS) were determined using the Kaplan–Meier plotter online tool.

In total, 69 upregulated and 65 downregulated genes were identified. Based on the PPI network of the DEGs, 20 genes were considered hub genes. RUNX2 silencing significantly downregulated the FN1 expression in MGC-803 cells. High expression of RUNX2 and low expression of FN1 were associated with long survival time in diffuse, poorly differentiated, and lymph node-positive GC.

High RUNX2 and FN1 expression were associated with poor OS in patients with GC. RUNX2 can negatively regulate the secretion of FN1, and both genes may serve as promising targets for GC treatment.

• FN1
• RUNX2
• bioinformatics analysis
• gastric cancer
• prognosis

• cardiac repair
• cell reprogramming
• in situ transfection
• naked plasmid delivery
• polyurethane hydrogels

• Arthroscopy/methods
• Bursa, Synovial/pathology
• Cell Differentiation
• Female
• Humans
• Male
• Mesenchymal Stem Cells/cytology
• Middle Aged
• Rotator Cuff/pathology
• Rotator Cuff/surgery
• Rotator Cuff Injuries/diagnosis
• Rotator Cuff Injuries/surgery