The in vivo and in vitro studies indicated that the PI3K/Akt cell signaling pathway is involved in the inhibition of osteoporosis through promoting osteoblast proliferation, differentiation and bone formation.

Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

Modern pharmacological studies revealed that Celastrol exhibits anti‑inflammation, anti‑bacteria, anti‑virus, anti‑fertility, insect‑resistance functions and has been used for the treatment of rheumatism, rheumatoid arthritis, blood diseases, skin diseases and agricultural insecticide. The present study aimed to investigate the effects of Celastrol on glucocorticoid‑induced osteoporosis (GIOP) and the underlying molecular mechanisms. The findings of the current study revealed that Celastrol reduced body weight, urine calcium/creatinine, tartrate‑resistant acid phosphatase 5b, C‑terminal telopeptide of type I collagen, and induced osteocalcin in GIOP rats. In addition, alkaline phosphatase, triiodothyronine receptor auxiliary protein and cathepsin K mRNA expression levels were effectively suppressed, and osteocalcin, bone morphogenetic protein 2, type I collagen and runt‑related transcription factor 2 mRNA expression levels were effectively induced in osteoporosis rats treated with Celastrol. Celastrol inhibited prostaglandin E2 and caspase‑3 protein expression levels, and induced phosphoinositol 3‑kinase (PI3K), phosphorylated‑protein kinase B (AKT) and glycogen synthase kinase‑3 phosphorylation, Wnt and β‑catenin protein expression in GIOP rats. The present study demonstrated that Celastrol may inhibit GIOP in rats via the PI3K/AKT and Wnt signaling pathways.

Experiments have demonstrated the regulation of long noncoding RNA (lncRNA) in tuberculosis (TB), and negative pressure treatment has been associated with the alleviation of TB. Here, we investigated the interaction of negative pressure and the lncRNA X‐inactive specific transcript (XIST) in modulating Mycobacterium tuberculosis (MTB) infection. Initially, we established an in vitro cell model of MTB infection and an in vivo mouse model of MTB infection, followed by treatment with negative pressure. Then, we examined the expression of XIST, followed by analysis of the downstream miRNA of XIST. XIST was overexpressed or underexpressed through cell transfection to examine its effects on macrophage polarization via the miR–125b–5p/A2 axis. The MTB models were characterized by upregulated XIST and downregulated miR‐125b‐5p. XIST bound to miR‐125b‐5p, leading to its downregulation, and thus causing higher MTB survival in an ESAT‐6–dependent manner. Additionally, negative pressure treatment decreased MTB‐driven XIST expression through downregulation of A20 (an NF‐κB repressor) via miR‐125b‐5 expression, promoting the M1 polarization program in macrophages through activation of the NF‐κB pathway. In summary, negative pressure treatment after MTB infection can promote the polarization of macrophages to the proinflammatory M1 phenotype by regulating the XIST/miR–125b–5p/A20/NF–κB axis.

Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, anti‑oxidation, anti‑inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were used to analyze runt‑related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression. The protective effect of EGCG against secondary osteoporosis was examined and its potential mechanism was analyzed. Treatment with EGCG significantly decreased serum calcium, urinary calcium, body weight and body fat, and increased leptin levels in mice with secondary osteoporosis. In addition, EGCG treatment significantly inhibited the structure score of articular cartilage and cancellous bone in proximal tibia metaphysis in mice with secondary osteoporosis. Treatment also significantly decreased alkaline phosphatase activity, runt‑related transcription factor 2 and osterix mRNA expression. EGCG also significantly induced the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression in mice with secondary osteoporosis. Taken together, these results suggest that EGCG may be a possible new drug in clinical settings.