A novel repair strategy using knotless squeeze anchors for lumbar disc herniation with endplate junction lesions under biportal endoscopic spinal surgery.

BACKGROUND: Annulus fibrosus-endplate (AF-EP) junction lesions are important determinants for lumbar disc herniation (LDH). Utilizing biportal endoscopic spinal surgery (BESS), we introduce a novel repair method using bioabsorbable PushLock anchors with suture fibers to stretch disconnected AF tissues to the vertebral cortex. METHODS: The viewing and working portals are established to excise herniated disc materials causing radiculopathy. Through the working portal, a suture strand is passed through the intact AF tissue near the lesion and retrieved using the Suture Crossing Device. Then, the knotless suture limbs are secured into the cortical bone socket of the vertebral body with a PushLock anchor. CONCLUSION: The procedure is a simple, safe, and feasible knotless suturing technique for the treatment of LDH with AF-EP junction lesions.

A novel missense COL9A3 variant in a pedigree with multiple lumbar disc herniation.

Trp3 allele in COL9A3 gene has been widely studied in populations with intervertebral disc disease. We identified a novel pathogenic variant in COL9A3 gene in a pedigree with multiple lumbar disc herniation (LDH). The proband was a 14-year-old boy who developed LDH at the L4/5 and L5/S1 spinal segments. His father, paternal aunt and grandfather were diagnosed with LDH at an age of 35, 30 and 23, respectively. By applying whole exome sequencing, a heterozygous missense variant (c.1150C > T, p.Arg384Trp) in COL9A3 was identified. According to the ACMG guidelines, this variant is predicted to be pathogenic. In addition, prediction tools found COL9A3 protein of this variant a reduced stability, some changed charge properties, and an altered spatial conformation. Findings expanded the mutational spectrum of LDH and contributed to the understanding of COL9A3 in the pathogenesis of LDH.

Lumbar disc herniation in juveniles: A case-control study of MRI characteristics and etiological insights.

Lumbar disc herniation (LDH) is rare in juveniles. LDH occurring at age 20 years or younger is referred to as juvenile disc herniation (JDH). While adult LDH is regarded as an advanced stage of disc degeneration, it remains unclear why intervertebral discs rupture in youth. This study aimed to characterize magnetic resonance imaging (MRI) findings of JDH and investigate possible etiological factors. From 2013 to 2020, JDH patients and controls were identified and interviewed to assess demographics, general lifestyles, and family histories. MRIs were evaluated for disc degeneration, epiphyseal ring separation, Modic changes and endplate lesions. The relationships between JDH and suspected risk factors were examined. A total of 297 JDH patients (199 boys and 98 girls, age 17.3 ± 2.1 years) and 185 controls (age 17.1 ± 2.4 years) were studied. Age, body mass index, exposures to daily physical labor, regular exercise, and daily sitting time were similar between JDH cases and controls. A family medical history of serious back pain was more common in JDH patients than in controls (59.4% vs. 26.5%, p < 0.001), as well as family history of clinically established LDH (45.0% vs. 12.4%, p < 0.001). Epiphyseal ring separation was identified in 102 (29.2%) herniated discs in 91 (36.4%) JDH patients, while occurring in only 5 (1.4%) control participants (p < 0.001). Overall, severe disc degeneration was not a prominent finding in JDH patients. In conclusion, epiphyseal ring separation was a common magnetic resonance feature in JDH. Findings suggest a genetically mediated developmental model of JDH, rather than a model of premature disc degeneration.

Arbutin-modified microspheres prevent osteoarthritis progression by mobilizing local anti-inflammatory and antioxidant responses.

Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome (GM-Lipo@ARB) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1ß-treated arthritic chondrocytes. Moreover, the synthesized GM-Lipo@ARB microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of GM-Lipo@ARB can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, GM-Lipo@ARB, and demonstrated that this compound may be used as an alternative therapeutics for treating OA.

ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies.

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both in vitro and in vivo. Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway-based modulations showed great potential in future therapeutic strategies for OA.

CXCR4-mediated signaling regulates autophagy and influences acute myeloid leukemia cell survival and drug resistance.

CXCR4 surface expression is considered an independent prognostic factor for disease relapse and survival in acute myeloid leukemia (AML) patients. Herein, we investigated targetable autophagy-related mechanisms of CXCR4 for AML therapy. Our experiments show that activation of CXCR4 signaling in AML cells increases autophagic activity and decreases cytarabine-induced apoptosis. Accordingly, combined use of autophagy inhibitors significantly increased the sensitivity of AML cells to cytarabine in vitro and in vivo. Moreover, expression of autophagy-related protein SIRT1 was correlated with SDF-1α-CXCR4 signaling, which interacts with autophagy proteins, such as ATG5 and LC3. Furthermore, in primary human AML samples, high CXCR4 expression was associated with elevated expression levels of SIRT1 and other autophagy-related proteins. Collectively, our data suggest new roles of SDF-1α-CXCR4 signaling on autophagy induction in AML cells, which further promoted their survival under stress. Targeting the SDF-1α-CXCR4-autophagy signaling may contribute to an enhanced efficacy of active treatments.