Intervertebral disc degeneration (IVDD) remains a clinical challenge and requires more effective therapeutic targets. Long noncoding RNAs (lncRNAs) have emerged as critical modulators of multiple biological processes, such as cell proliferation and extracellular matrix (ECM) remodeling. Accordingly, the current study sets out to explore the influence of the lncRNA growth arrest‐specific 5 (GAS5) on IVDD and investigate the possible involvement of microRNA‐17‐3p (miR‐17‐3p)/Angiopoietin‐2 (Ang‐2) axis. Firstly, the expression patterns of GAS5, miR‐17‐3p, and Ang‐2 were characterized by RNA quantification from the isolated human degenerative nucleus pulposus (NP) tissues. miR‐17‐3p was found to express at an abnormal low level while GAS5 and Ang‐2 expressed at aberrant high level in the human degenerative NP tissues. Utilizing dual‐luciferase reporter, RNA immunoprecipitation, and pull‐down assays, GAS5 was found to competitively bound to miR‐17‐3p and further upregulate the expression of Ang‐2, a target gene of miR‐17‐3p. Employing gain‐ and loss‐of‐function approaches, their expressions were altered in human degenerative nucleus pulposus cells (NPCs), followed by IL‐1β treatment, in order to identify their roles in NP cell proliferation, apoptosis, and ECM metabolism. Silencing of GAS5 expression restrained the levels of cleaved caspase‐3, cleaved caspase‐7, cleaved caspase‐9, MMP3, MMP13, ADAMTS4, and ADAMTS5 and increased collagen II and aggrecan levels. In vitro experiments also revealed that GAS5 depletion inhibited apoptosis and ECM degradation in HDNPCs, while elevating the proliferation through downregulation of Ang‐2 by increasing miR‐17‐3p. Furthermore, in vivo data further validated that either GAS5 silencing or miR‐17‐3p reexpression alleviated IVDD degree with the help of IVDD mouse models. Altogether, our findings substantiated that downregulation of GAS5 reduced NPC apoptosis and promoted ECM remodeling, ultimately ameliorating the IVDD via miR‐17‐3p‐dependent inhibition of Ang‐2. We hope our discoveries offer a fresh molecular insight that can aid the development of novel therapies against IVDD.

Recent studies indicate that uPAR acts a crucial part in cell migration and the modulation of bone homeostasis. As a natural serine protease inhibitor, ulinastatin owns the capacity to reduce proinflammatory factors, downregulate the activation of NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways. Osteoclastogenesis has been demonstrated to be related with low-grade inflammation which involves cell migration, thus we speculate that ulinastatin may have a certain kind of impact on uPAR so as to be a potential inhibiting agent of osteoclastogenesis. In this research, we investigated the role which ulinastatin plays in RANKL-induced osteoclastogenesis both in vivo and in vitro. Ulinastatin inhibited osteoclast formation and bone resorption in a dose-dependent manner in primary bone marrow-derived macrophages (BMMs), and knockdown of uPAR could completely repress the formation of osteoclasts. At the molecular level, ulinastatin suppressed RANKL-induced activation of cathepsin K, TRAP, nuclear factor-κB (NF-κB) and MAPKs, and decreased the expression of uPAR. At the meantime, ulinastatin also decreased the expression of osteoclast marker genes, including cathepsin K, TRAP, RANK, and NFATc1. Besides, ulinastatin prevented bone loss in ovariectomized C57 mice by inhibiting the formation of osteoclasts. To sum up, this research confirmed that ulinastatin has the ability to inhibit osteoclastogenesis and prevent bone loss, and uPAR plays a crucial role in that process. Therefore, ulinastatin could be chosen as an effective alternative therapeutics for osteoclast-related diseases.

The nail is a continuous skin appendage. Cells located around the nails, which display coordinated homeostatic dynamics and release a flow of stem cells in response to regeneration, have been identified in mice. However, very few studies regarding human nail stem cells exist in the literature. Using specimens isolated from humans, we detected an unreported population of cells within the basal layer of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail root. These cells were multi-expressing and expressed stem cell markers, such as keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very similar to mouse nail stem cells in terms of cell marker expression and their location within the nail. We also found that the putative nail stem cells maintained their abundance with advancing age, but cell proliferation and nail growth rate were decreased on comparison of young and aged specimens. To summarize, we found a putative population of stem cells in postnatal human nails located at NPFs and the nail matrix. These cells may have potential for cell differentiation and be capable of responding to injury, and were retained, but may be hypofunctional during aging.

Background: The number of children with polydactyly seen in our clinic is increasing. In addition to genetic factors, an influence of environmental effects during pregnancy is becoming increasingly apparent; however, epidemiological data on these effects are lacking. Methods: This hospital-based, case-control study enrolled 143 patients with polydactyly and 286 control patients with no genetic diseases, to evaluate the association between maternal exposure to a textile factory environment during pregnancy and the likelihood of giving birth to a child with polydactyly. Results: Maternal exposure to a textile factory environment during pregnancy was associated with an increased risk of giving birth to a child with polydactyly (exposure to textile factory environment: unadjusted odds ratio (OR) 3.31, 95% confidence interval (CI) 1.75–6.27, p = 0.0002; work seniority of exposed occupation: unadjusted OR 1.28, 95% CI 1.13–1.47, p = 0.0002). Covariate screening indicated that certain risk factors (family monthly income per capita, mother’s emotional state during pregnancy, colporrhagia, passive smoking, smoking, and history of consanguineous marriage) were potential confounding factors. After adjusting for these variables, the OR of exposure to a textile factory environment remained significant (exposure to textile factory environment: adjusted OR 3.08, 95% CI 1.32–7.19, p = 0.0094; work seniority of exposed occupation: adjusted OR 1.58, 95% CI 1.20–2.08, p = 0.0010). The risk of polydactyly increased with the number of years of employment. Conclusions: Maternal exposure to a textile factory environment appears to be a risk factor for polydactyly in newborns.