Search Results (8)

Apoptosis plays a crucial role in the progression of intervertebral disc degeneration (IVDD), a significant cause of chronic low back pain. This review explores disc cell apoptosis’s cellular and molecular mechanisms, focusing on nucleus pulposus, annulus fibrosus, and cartilage endplates cells. Apoptotic pathways—intrinsic (mitochondrial), extrinsic (death receptor-mediated), ER stress-mediated, and autophagy-related—are activated by oxidative stress, inflammation, mechanical load, and metabolic disturbances like hyperglycemia. Diabetes exacerbates disc cell apoptosis through AGE-RAGE signaling and mitochondrial dysfunction. Inflammation further amplifies apoptotic cascades via cytokine signaling and ROS generation. The review also examines emerging therapeutic strategies, including antioxidants (e.g., MitoQ, resveratrol), anti-inflammatory agents (e.g., cytokine inhibitors), autophagy modulators (e.g., rapamycin, metformin), and stem cell and gene therapies. While promising preclinical results exist, challenges such as poor bioavailability and clinical translation remain. Enhanced understanding of apoptosis pathways informs future cellular preservation and matrix integrity treatments. Based on a comprehensive literature search from 2000 to 2025, this narrative review synthesizes current knowledge, identifies knowledge gaps, and discusses translational potential. Our findings support a paradigm shift toward mechanism-based therapies that address the root cause of IVDD rather than symptomatic relief alone. Full article

Purpose: We assessed the feasibility of qualitative, semiquantitative, and multiparametric quantitative magnetic resonance imaging (MRI) using a three-dimensional (3D) ultrashort echo time (3D-UTE) sequence together with 2D-T2 and 3D-T1 mapping sequences to evaluate normal and pathological discovertebral complexes (DVCs). We assessed the disc (nucleus pulposus [NP] and annulus fibrosus [AF]), vertebral endplate (cartilage endplate [CEP] and growth plate [GP]), and subchondral bone (SB) using a rat model of degenerative disc disease (DDD). We also assessed whether this complete MRI cartography can improve the monitoring of DDD. Methods: DDD was induced by percutaneous disc trituration and collagenase injection of the tail. Then, the animals were imaged at 4.7T. The adjacent disc served as the control. The MRI protocol was performed at baseline and each week (W) postoperatively for 2 weeks. Visual analysis and signal intensity measurements from the 3D-UTE images, as well as T2 and T1 measurements, were carried out in all DVC portions. Histological analysis with hematoxylin–eosin and Masson trichrome staining was performed following euthanization of the rats at 2 weeks and the results were compared to the MRI findings. Results: Complete qualitative identification of the normal zonal anatomy of the DVC, including the AF, CEP, and GP, was achieved using the 3D-UTE sequence. Quantitative measurements of the signal-to-noise ratio in the AF and NP enabled healthy DVCs to be distinguished from surgery-induced DDD, based on an increase in these values post-surgery. The 2D-T2 mapping results showed a significant increase in the T2 values of the AF and a decrease in the values of the NP between the baseline and W1 and W2 postoperatively (p < 0.001). In the 3D-T1 mapping, there was a significant decrease in the T1 values of the AF and NP between baseline and W1 and W2 postoperatively in immature rats (p < 0.01). This variation in T1 and T2 over time was consistent with the results of the 3D-UTE sequence. Conclusions: Use of the 3D-UTE sequence enabled a complete, robust, and reproducible visualization of DVC anatomy in both immature and mature rats under both normal and pathological conditions. The findings were supported quantitatively by the T2 and T1 mapping sequences and histologically. This sequence is therefore of prime interest in spinal imaging and should be regularly be performed. Full article

Background: Chronic low back pain (LBP) has been associated with intervertebral disc (IVD) degeneration, but its association with abnormal morphology at the discovertebral junction (DVJ) is unclear. The goal of this study was to evaluate the DVJ morphology in asymptomatic (Asx) and symptomatic (Sx) subjects for LBP using ultrashort echo time (UTE) MRI. Methods: We recruited 42 subjects (12 Asx and 32 Sx). Lumbar IVD degeneration was assessed using Pfirrmann grading (1 to 5), while the abnormality of DVJ (0 = normal; 1 = focal; 2 = broad abnormality) was assessed using UTE MRI. The effects of LBP and level on the mean IVD and DVJ grades, the correlation between IVD and DVJ grade, and the effect of LBP and age on the number of abnormal DVJs within a subject were determined. Results: IVD grade was higher in Sx subjects (p = 0.013), varying with disc level (p = 0.033), adjusted for age (p < 0.01). Similarly, DVJ grade was also significantly higher in Sx subjects (p = 0.001), but it did not vary with DVJ level (p = 0.7), adjusted for age (p = 0.5). There was a weak positive (rho = 0.344; p < 0.001) correlation between DVJ and IVD grade. The total number of abnormal DVJs within a subject was higher in Sx subjects (p < 0.001), but not with respect to age (p = 0.6) due to a large spread throughout the age range. Conclusions: These results demonstrate the feasibility of using in vivo UTE MRI of the lumbar spine to evaluate the DVJ and the correlation of DVJ with LBP. This study highlights the need for a better understanding of DVJ pathology and the inclusion of DVJ assessment in routine lumbar MRI. Full article

Introduction: The disco-vertebral junction (DVJ) of the lumbar spine contains thin structures with short T2 values, including the cartilaginous endplate (CEP) sandwiched between the bony vertebral endplate (VEP) and the nucleus pulposus (NP). We previously demonstrated that ultrashort-echo-time (UTE) MRI, compared to conventional MRI, is able to depict the tissues at the DVJ with improved contrast. In this study, we sought to further optimize UTE MRI by characterizing the contrast-to-noise ratio (CNR) of these tissues when either single echo or echo subtraction images are used and with varying echo times (TEs). Methods: In four cadaveric lumbar spines, we acquired 3D Cones (a UTE sequence) images at varying TEs from 0.032 ms to 16 ms. Additionally, spin echo T1- and T2-weighted images were acquired. The CNRs of CEP-NP and CEP-VEP were measured in all source images and 3D Cones echo subtraction images. Results: In the spin echo images, it was challenging to distinguish the CEP from the VEP, as both had low signal intensity. However, the 3D Cones source images at the shortest TE of 0.032 ms provided an excellent contrast between the CEP and the VEP. As the TE increased, the contrast decreased in the source images. In contrast, the 3D Cones echo subtraction images showed increasing CNR values as the second TE increased, reaching statistical significance when the second TE was above 10 ms (p < 0.05). Conclusions: Our study highlights the feasibility of incorporating UTE MRI for the evaluation of the DVJ and its advantages over conventional spin echo sequences for improving the contrast between the CEP and adjacent tissues. Additionally, modulation of the contrast for the target tissues can be achieved using either source images or subtraction images, as well as by varying the echo times. Full article

Introduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. Methods: Gene expression of TLR1–10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. Results: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. Conclusions: The expression of TLR1–10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC. Full article

This paper aims to report clinical, laboratory, radiographic, and pathological features in a case of cervical vertebral stenotic myelopathy (CVSM) affecting a 4-month-old Nelore calf for the first time. During physical examination, the calf could stand if assisted when lifting by the tail but fallen to the ground when trying to walk. Attempts to flex and extend the neck to the right side failed. Radiographs findings consisted of reduced intervertebral spaces, and misalignments between the endplates, more evident between the C3 and C4 vertebrae, resulting in narrowing of the spinal canal and compression of the spinal cord. Grossly, C4 showed cranial articular surface malformation, abnormal metaphyseal growth plate development, reduced vertebral body size and deformity. Histologically, C4 showed an abnormal vertebral bone development characterized by moderate replacement of trabecular bone by fibrous tissues, multifocal areas of dystrophic hyaline cartilage development, and cartilaginous growth failure along the metaphyseal growth plate. Cervical spinal cord within the stenotic vertebral canal showed swollen neurons with central chromatolysis, areas of Wallerian degeneration, and necrotic debris. In contrast with the well-known Wobbler syndrome in horses, the etiology of CVSM in cattle remains undetermined, and further genetic and pathological studies must be conducted to elucidate it. Full article

This paper aims to provide a comprehensive review of the changing role of hepatocyte growth factor (HGF) signaling in the healthy and diseased synovial joint and spine. HGF is a multifunctional growth factor that, like its specific receptor c-Met, is widely expressed in several bone and joint tissues. HGF has profound effects on cell survival and proliferation, matrix metabolism, inflammatory response, and neurotrophic action. HGF plays an important role in normal bone and cartilage turnover. Changes in HGF/c-Met have also been linked to pathophysiological changes in degenerative joint diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IDD). A therapeutic role of HGF has been proposed in the regeneration of osteoarticular tissues. HGF also influences bone remodeling and peripheral nerve activity. Studies aimed at elucidating the changing role of HGF/c-Met signaling in OA and IDD at different pathophysiological stages, and their specific molecular mechanisms are needed. Such studies will contribute to safe and effective HGF/c-Met signaling-based treatments for OA and IDD. Full article

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies. Full article