Development of osteoarthritis (OA) correlates with epigenetic alteration in chondrocytes. H3K27me3 demethylase UTX is known to regulate tissue homeostasis, but its role in the homeostasis of articulating joint tissue is poorly understood. Forced UTX expression upregulated H3K27me3 enrichment at the Sox9 promoter region to inhibit key extracellular matrix (ECM) molecules, like e.g. type II collagen, aggrecan, and glycosaminoglycans in articular chondrocytes. Utx loss in vitro altered the H3K27me3-binding epigenomic landscape, which contributes to mitochondrial activity, cellular senescence, and cartilage development. Functional target genes of Utx comprise insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription, but inhibited Eed and Suz12 expression. Igf2 inhibition or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at the Sox9 promoter, compromising Utx loss-induced ECM overproduction. Overexpression of Utx in murine knee joints aggravated OA development, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss. Transgenic mice with a chondrocytespecific Utx knockout develop thicker articular cartilage as compared to wild-type controls and show fewer gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced joint injury. In summary, UTX represses chondrocytic activity and accelerates cartilage degradation during OA, while Utx loss promotes cartilage integrity through epigenetic stimulation of mitochondrial biogenesis and Igf2 transcription. This highlights a novel noncanonical role of Utx that regulates articular chondrocyte anabolism and OA development.

Introduction and Objective

Senescent bone cell overburden accelerates osteoporosis. Epigenetic alteration, including microRNA signalling and DND methylation, is one of prominent features of cellular senescence. This study aimed to investigate what role microRNA-29a signalling may play in the development of senile osteoporosis.

Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

The effects of Hypericum perforatum on nerve regeneration after sciatic nerve injury have not yet been evaluated in all its aspects yet. In this experimental study, the effect of Hypericum perforatum on injured nerve tissue was histologically and biochemically investigated. Motor functional healing was surveyed by gait analysis.

Rats were divided into 3 groups: Group I (n=8) was intact control group and no intervention and treatment was applied to this group. Group II (n=16) was surgical control group and Group III (n=16) was Hypericum perforatum group. After the operation, while any treatment was performed on Group II, 30 mg/kg dose Hypericum perforatum extract was intraperitoneally administered to the Group III per day for 8 weeks from the 1^st day of post-op. Gait analysis was made to all rats for functional evaluation at 2^nd, 3^rd, 4^th, 6^th and 8^th weeks, and sciatic functional index (SFI) was evaluated. At the end of the eighth week, sciatic nerve tissue samples were taken from the sacrificed rats. Tissues were examined biochemically, histologically and immnohistochemically. Malondialdehyde (MDA) as an indicator of oxidative stress and main antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)] levels were biochemically measured. The nerve degeneration and regeneration were histologically viewed, and also cell count was immnohistochemically done by having done anti-S100 staining.

It was seen that measurement results of SFI were statistically significantly difference between groups (p<0,001). In the sciatic nerve tissue samples taken from the rats, it was not determined a statistically significant difference between MDA, SOD, GPx and CAT levels detected by ELISA method (p>0,05). In the histological evaluation, it was seen that Hypericum perforatum affected positively the regeneration and immunohistochemically, it was found a statistically significant difference between the anti-S-100 positive cell numbers.

The obtained results in this study show that; Hypericum perforatum, which was intraperitoneally administered on rats subjected to nerve injury, has affected positively the nerve regeneration and it can also provide an insight to future studies.

Objectives

The cytotoxicity induced by cobalt ions (Co²⁺) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co²⁺ and Co-NPs on liver cells, and explain further the potential mechanisms.

Objectives

Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co²⁺) during wear of MOM hip implants, but the toxic mechanism is not clear.