Intervertebral disc degeneration (IDD) is associated with the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in the development of IDD. Using bioinformatics prediction, we hereby sought to identify the lncRNAs that regulate the expression of microRNA-146a-5p (miR-146a-5p), an IDD-related inflammatory factor. Our study demonstrated that lncRNA HCG18 acted as an endogenous sponge to down-regulate miR-146a-5p expression in the NP cells by directly binding to miR-146a-5p. In addition, HCG18 expression was up-regulated in the patients with IDD, bulging or herniated discs, and its level was positively correlated with the disc degeneration grade. In vitro, miR-146a-5p up-regulation HCG18 retarded the growth of NP cells by decreasing S phase of cell cycle, inducing cell apoptosis, recruitment of macrophages and hypercalcification. Conversely, down-regulation of miR-146a-5p exerted opposite effects. Furthermore, we elucidated that TRAF6, a target gene by miR-146a-5p, was modulated by HCG18 expression. Restore of TRAF6 expression by virus infection reserved the effect of HCG18 on the NP cells. Altogether, our data indicated that HCG18 suppressed the growth of NP cells and promoted the IDD development via the miR-146a-5p/TRAF6/NFκB axis.

Surface-modified metal implants incorporating different ions have been employed in the biomedical field as bioactive dental implants with good osseointegration properties. However, the molecular mechanism through which surface coatings exert the biological activity is not fully understood, and the effects have been difficult to achieve, especially in the osteopenic bone. In this study, We examined the effect of zinc-modified calcium silicate coatings with two different Zn contents to induce osteogenic differentiation of rat bone marrow-derived pericytes (BM-PCs) and osteogenetic efficiency in ovariectomised rabbits. Ti-6Al-4V with zinc-modified calcium silicate coatings not only enhanced proliferation but also promoted osteogenic differentiation and mineralized matrix deposition of rat BM-PCs as the zinc content and culture time increased in vitro. The associated molecular mechanisms were investigated by Q-PCR and Western blotting, revealing that TGF-β/Smad signaling pathway plays a direct and significant role in regulating BM-PCs osteoblastic differentiation on Zn-modified coatings. Furthermore, in vivo results that revealed Zn-modified calcium silicate coatings significantly promoted new bone formation around the implant surface in osteopenic rabbits as the Zn content and exposure time increased. Therefore, Zn-modified calcium silicate coatings can improve implant osseointegration in the condition of osteopenia, which may be beneficial for patients suffering from osteoporosis-related fractures.

Ankylosing spondylitis (AS) is a complex disease characterized by inflammation and ankylosis primarily at the cartilage–bone interface. The disease is more common in young males and risk factors include both genetic and environmental. While the pathogenesis of AS is not completely understood, it is thought to be an immune-mediated disease involving inflammatory cellular infiltrates, and human leukocyte antigen-B27. Currently, there is no specific diagnostic technique available for this disease; therefore conventional diagnostic approaches such as clinical symptoms, laboratory tests and imaging techniques are used. There are various review papers that have been published on conventional treatment approaches, and in this review work, we focus on the more promising nanomedicine-based treatment modalities to move this field forward.

Objective Special hypoxic and hypertonic microenvironment in intervertebral discs (IVDs) decreases the treatment effect of cell transplantation. We investigated the hypothesis that hypoxic preconditioning (HP) could improve the therapeutic effect of bone mesenchymal stem cells (BMSCs) to IVD degeneration. Methods BMSCs from green fluorescent protein-transgenic rats were pretreated with cobalt chloride (CoCl2, 100 μM, 24 h) for hypoxic conditions in vitro. Apoptosis (related pathways of caspase-3 and bcl-2) and migration (related pathways of HIF-1α and CXCR4) were detected in BMSCs. In vivo, BMSCs and HP BMSCs (H-BMSCs) were injected into the rat model of IVD degeneration. The IVD height, survival, migration, and differentiation of transplanted BMSCs and matrix protein expression (collagen II, aggrecan, and MMP-13) were tested. Results H-BMSCs could extensively decrease IVD degeneration by increasing IVD height and collagen II and aggrecan expressions when compared with BMSCs. Significantly, more GFP-positive BMSCs were observed in the nucleus pulposus and annulus fibrosus regions of IVD. HP could significantly decrease BMSC apoptosis (activating bcl-2 and inhibiting caspase-3) and improve BMSC migration (increasing HIF-1α and CXCR4) in vitro. Conclusion HP could significantly enhance the capacity of BMSCs to repair DDD by increasing the survival and migration of implanted cells and increasing matrix protein expression.

Background: To compare standalone oblique lateral interbody fusion (OLIF) vs. OLIF combined with posterior bilateral percutaneous pedicle screw fixation (OLIF combined) for the treatment of lumbar spondylolisthesis. Methods: This was a retrospective study of patients who underwent standalone OLIF or combined OLIF between 07/2014 and 08/2017 at two hospitals in China. Direct decompressions were not performed. Visual analog scale (VAS), Oswestry Disability Index (ODI), satisfaction rate, anterior/posterior disc heights (DH), foraminal height (FH), foraminal width (FW), cage subsidence, cage retropulsion, fusion rate, and complications were analyzed. All imaging examinations were read independently by two physicians and the mean measurements were used for analysis. Results: A total of 73 patients were included: 32 with standalone OLIF and 41 with combined OLIF. The total complication rate was 25.0% with standalone OLIF and 26.8% with combined OLIF. There were no differences in VAS and ODI scores by 2 years of follow-up, but the scores were better with standalone OLIF at 1 week and 3 months (P < 0.05). PDH and FW was smaller in the combined OLIF group compared with the standalone OLIF group before and after surgery (all P < 0.05). There were significant differences in FH before surgery and at 1 week and 3 months between the two groups (all P < 0.05), but the difference disappeared by 2 years (P = 0.111). Cage subsidence occurred in 7.3% (3/41) and 7.3% (3/41) of the patients at 3 and 24 months, respectively, in the combined OLIF group, compared with 6.3% (2/32) and 15.6% (5/32), respectively, in the standalone OLIF group at the same time points (P = 0.287). There was no cage retropulsion in both groups at 2 years. The fusion rate was 85.4%(35/41) in the combined OLIF group and 84.4% (27/32) in the standalone OLIF group at 3 months(P = 0.669). At 24 months, the fusion rate was 100.0% in the combined OLIF group and 93.8% (30/32) in the standalone OLIF group (P = 0.066).