There is a growing perception that long non-coding RNAs (lncRNAs) modulate cellular function. In this study, we analyzed the role of the lncRNA HOTAIR in mesenchymal stem cells (MSCs) with particular focus on senescence-associated changes in gene expression and DNA-methylation (DNAm). HOTAIR binding sites were enriched at genomic regions that become hypermethylated with increasing cell culture passage. Overexpression and knockdown of HOTAIR inhibited or stimulated adipogenic differentiation of MSCs, respectively. Modification of HOTAIR expression evoked only very moderate effects on gene expression, particularly of polycomb group target genes. Furthermore, overexpression and knockdown of HOTAIR resulted in DNAm changes at HOTAIR binding sites. Five potential triple helix forming domains were predicted within the HOTAIR sequence based on reverse Hoogsteen hydrogen bonds. Notably, the predicted triple helix target sites for these HOTAIR domains were also enriched in differentially expressed genes and close to DNAm changes upon modulation of HOTAIR. Electrophoretic mobility shift assays provided further evidence that HOTAIR domains form RNA–DNA–DNA triplexes with predicted target sites. Our results demonstrate that HOTAIR impacts on differentiation of MSCs and that it is associated with senescence-associated DNAm. Targeting of epigenetic modifiers to relevant loci in the genome may involve triple helix formation with HOTAIR.

Long-term and stable fixation of implants is one of the most important points for a successful orthopedic surgery in the field of endoprosthesis. Osseointegration (OI), functional connection between bone and implants, is considered as a pivotal process of cementless implant fixation and integration, respectively. OI is affected by various factors of which the property of implants is of high significance. The modification of implants surface for better OI has raised increasing attention in modern orthopedic medicine. Here, the process of OI and the interactions between implants and ambient bone tissues were emblazed. The knowledge regarding the contemporary surface modification strategies was systematically analyzed and reviewed, including materials used for the fabrication of implants, advanced modification techniques, and key factors in the design of porous implants structure. We discussed the superiority of current surface modification programs and concluded that the problems remain to be solved. The primary intention of this systematic review is to provide comprehensive reference information and an extensive overview for better fabrication and design of orthopedic implants. K E Y W O R D Sbiomaterials, orthopedic implants, osseointegration, surface modification

Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application.

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