• Animal models
• Caudal disc puncture
• Chemonucleolysis
• Intervertebral disc degeneration
• Lumbar spine instability
• Microenvironment

• Animal model
• Grading
• Intervertebral disc degeneration
• Magnetic resonance imaging
• Microcomputed tomography

• Animals
• Intervertebral Disc Degeneration/diagnostic imaging
• Intervertebral Disc Degeneration/etiology
• Intervertebral Disc Degeneration/pathology
• Magnetic Resonance Imaging/methods
• Rats, Sprague-Dawley
• Disease Models, Animal
• Male
• Rats
• Disease Progression
• Needles
• Punctures
• Intervertebral Disc/diagnostic imaging
• Intervertebral Disc/pathology
• X-Ray Microtomography/methods

• [2022] No.35 Shandong University of Chinese Medicine teaching master project
• 2021YFC1712805 National Key R&D Program of China
• 2021YFC1712805 National Key R&D Program of China
• 2021YFC1712805 National Key R&D Program of China
• 2021YFC1712805 National Key R&D Program of China
• 2023B1111030002 Guangdong Key R&D Program
• 2023B1111030002 Guangdong Key R&D Program
• 2022A0505020017 Provincial Science and Technology Plan Projects in Guangdong Province
• 2022A0505020017 Provincial Science and Technology Plan Projects in Guangdong Province
• GJHZ20210705141405015 Shenzhen International Collaborative Project
• National Key R&D Program of China
• Guangdong Key R&D Program
• SIAT Innovation Program for Excellent Young Researchers (2022)

• animal model
• annulus fibrosus injury
• astrocyte
• discogenic pain
• dorsal root ganglion
• intervertebral disc degeneration
• macrophage
• microglia
• satellite glial cell
• spinal cord

• Rats
• Animals
• Annulus Fibrosus
• Intervertebral Disc/injuries
• Neuroinflammatory Diseases
• Ganglia, Spinal
• Intervertebral Disc Degeneration/complications
• Chronic Pain/complications
• Spinal Cord

• R01 AR078857 NIAMS NIH HHS
• R01 AR080096 NIAMS NIH HHS
• R01AR078857 NIAMS NIH HHS
• P30AR079206 NIAMS NIH HHS

• AOSDIA2019-057 AO Foundation (AO)

A targeted injury to the mouse intervertebral disc (IVD) is often used to recapitulate the degenerative cascade of the human pathology. Since injuries can vary in magnitude and localization, it is critical to examine the effects of different injuries on IVD degeneration. We thus evaluated the degenerative progression resulting from either a partial- or full-width injury to the mouse lumbar IVD using contrast-enhanced micro-computed tomography and histological analyses. A lateral-retroperitoneal surgical approach was used to access the lumbar IVD, and the injuries to the IVD were produced by either incising one side of the annulus fibrosus or puncturing both sides of the annulus fibrosus. Female C57BL/6J mice of 3–4 months age were used in this study. They were divided into three groups to undergo partial-width, full-width, or sham injuries. The L5/6 and L6/S1 lumbar IVDs were surgically exposed, and then the L6/S1 IVDs were injured using either a surgical scalpel (partial-width) or a 33G needle (full-width), with the L5/6 serving as an internal control. These animals recovered and then euthanized at either 2-, 4-, or 8-weeks after surgery for evaluation. The IVDs were assessed for degeneration using contrast-enhanced microCT (CEµCT) and histological analysis. The high-resolution 3D CEµCT evaluation of the IVD confirmed that the respective injuries were localized within one side of the annulus fibrosus or spanned the full width of the IVD. The full-width injury caused significant deteriorations in the nucleus pulposus, annulus fibrous and at the interfaces after 2 weeks, which was sustained through the 8 weeks, while the partial width injury caused localized disruptions that remained limited to the annulus fibrosus. The use of CEµCT revealed distinct IVD degeneration profiles resulting from partial- and full-width injuries. The partial width injury may serve as an alternative model for IVD degeneration resulting from localized annulus fibrosus injuries.

• animal model
• biomaterials
• biomolecules
• cells
• intervertebral disc
• preclinical
• tissue engineering

Aims. Accumulating evidence reported that the microRNA (miRNA) took an important role in intervertebral disc degeneration (IDD). In this study, we revealed a novel miRNA regulatory mechanism in IDD. Main Methods. The miRNA microarray analyses of human degenerated and normal disc samples were employed to screen out the target miRNA. In vitro and in vivo experiments were conducted to verify the regulatory effect of miR-101-3p. Key Findings. The expression level of miR-101-3p was significantly decreased in the degenerated disc samples which were confirmed by qRT-PCR. Moreover, the miR-101-3p expression level was changed dynamically according to the disc degeneration grade. Upregulation of miR-101-3p expression level inhibited cell apoptosis. Furthermore, stanniocalcin-1 (STC1) was selected to be the target gene of miR-101-3p according to the bioinformatic algorithms. Mechanically, upregulation of miR-101-3p significantly decreased the expression of STC1, vascular endothelial growth factor (VEGF), and MAPK pathway expression levels. Therapeutically, in vivo experiment on IDD rat model illustrated that agomir-101-3p could effectively suspend IDD. Significance. Our findings demonstrated that miR-101-3p alleviated IDD process through the STC1/VEGF/MAPK pathway.

• animal model
• cGAS/STING signalling pathway
• intervertebral disc degeneration
• spread of inflammation
• vertebral inflammation-induced intervertebral disc degeneration model

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation.

• MSCs
• biomaterials
• inflammation
• intervertebral disc
• recruitment

• Animal experiment
• Endplate injury
• Intervertebral disc degeneration
• Vertebral body fracture

• Animals
• Fractures, Bone
• Intervertebral Disc
• Intervertebral Disc Degeneration/diagnostic imaging
• Lumbar Vertebrae
• Male
• Rats
• Rats, Sprague-Dawley
• Spinal Fractures

Many studies focused on the annulus fibrosus (AF) injury in rodent tail model for the intervertebral disk degeneration (IDD) research. However, previous studies caused tremendous injury of intervertebral disk (IVD) by penetrating whole disk. This study aimed to build a progressive IDD rodent tail model by a novel device for precise and minimally invasive puncture in AF. A precise puncture device was customized by 3D Printing Technique. 40 rodent tail IVDs were randomly grouped as follows: group A, non-puncture; group B, annulus needle puncture (ANP) for 4 week; group C, ANP for 8 week; and group D, ANP for 12 week. Pre- and post-puncture IVD height on radiographs and IVD signal intensity on T2 magnetic resonance imaging (MRI) were measured. Average bone density (ABD) on the end of coccygeal vertebrae between punctured disk was measured on the radiographs. Hematoxylin and eosin, TUNEL staining methods, immunofluorescence for cleaved-caspas3 and immunohistochemistry for aggrecan and collagen II were performed. Progressively and significantly increasing IVD height loss and degenerative grade were observed following the time points. The ABD was respectively, 81.20 ± 4.63 in group A, 83.93±3.18 in group B, 92.65 ± 4.32 in group C, 98.87 ± 6.69 in group D. In both group C and group D, there were significant differences with group A. In histology, increasing number of AF cells was noted in group B. In both group C and D, the fissures in AF were obviously observed, and a marked reduction of AF cells were also observed. In all ANP groups, there were significant decrease in number of NP cells, as well as aggrecan and collagen II contents. TUNEL assay showed cellular apoptosis were stimulated in all puncture group, especially in group D. A progressive IDD rat model could be standardly established by the micro-injury IVD puncture using a novel 3D printing device. This animal model provided a potential application for research of progressive hyperosteogeny following IDD development.

• 3D printing technique
• disk degeneration
• minimally invasive procedure
• rodent tail model
• vertebral hyperosteogeny

• histology
• histology grading scale
• histopathology
• intervertebral disc degeneration
• intervertebral disc regeneration
• rat model

• R01 AR057397 NIAMS NIH HHS
• R01 AR078857 NIAMS NIH HHS

• Animal model
• Cell migration
• Chemokine
• Chemokine receptor
• Disc degeneration
• Disc inflammation
• Small molecule antagonist

• Animals
• Cell Movement
• Chemokines, CC
• Inflammation/drug therapy
• Intervertebral Disc
• Intervertebral Disc Degeneration
• Rabbits
• Receptors, CCR1

• granulocyte-colony stimulating factor
• intervertebral disc degeneration
• needle puncture
• stromal cell derived factor-1α

• degeneration
• extracellular matrix

Conventional plain X-ray images of rats, the most common animals used as degeneration models, exhibit unclear vertebral structure and blurry intervertebral disc spaces due to their small size, slender vertebral bodies.

To apply molybdenum target X-ray photography in the evaluation of caudal intervertebral disc (IVD) degeneration in rat models.

Two types of rat caudal IVD degeneration models (needle-punctured model and endplate-destructed model) were established, and their effectiveness was verified using nuclear magnetic resonance imaging. Molybdenum target inspection and routine plain X-ray were then performed on these models. Additionally, four observers were assigned to measure the intervertebral height of degenerated segments on molybdenum target plain X-ray images and routine plain X-ray images, respectively. The degeneration was evaluated and statistical analysis was subsequently conducted.

Nine rats in the needle-punctured model and 10 rats in the endplate-destructed model were effective. Compared with routine plain X-ray images, molybdenum target plain X-ray images showed higher clarity, stronger contrast, as well as clearer and more accurate structural development. The McNemar test confirmed that the difference was statistically significant (P = 0.031). In the two models, the reliability of the intervertebral height measured by the four observers on routine plain X-ray images was poor (ICC < 0.4), while the data obtained from the molybdenum target plain X-ray images were more reliable.

Molybdenum target inspection can obtain clearer images and display fine calcification in the imaging evaluation of caudal IVD degeneration in rats, thus ensuring a more accurate evaluation of degeneration.

• Molybdenum target inspection
• Routine plain X-ray
• Intervertebral disc degeneration model
• Animal experiment
• Imaging analysis
• McNemar test

Inflammation is central in intervertebral disc (IVD) degeneration/regeneration mechanisms, and its balance is crucial to maintain tissue homeostasis. This work investigates the modulation of local and systemic inflammatory response associated with IVD degeneration/herniation by administration of PRO- versus ANTI-inflammatory treatments. Chitosan/poly-γ-glutamic acid nanocomplexes, known as pro-inflammatory (PRO), and soluble diclofenac, a non-steroidal anti-inflammatory drug (ANTI), were intradiscally administered in a rat IVD injury model, 24 h after lesion. Two weeks after administration, a reduction of disc height accompanied by hernia formation was observed. In the PRO-inflammatory treated group, IL-1β, IL-6 and COX-2 IVD gene expression were upregulated, and loss of nucleus pulposus (NP) structure and composition was observed. Systemically, lower T-cell frequency was observed in the lymph nodes (LN) and spleen (SP) of the PRO group, together with an increase in CD4+ T cells subset in the blood (BL) and LN. In contrast, the ANTI-group had higher proteoglycans/collagen ratio and collagen type 2 content in the NP, while an increase in the frequency of myeloid cells, M1 macrophages and activated macrophages (MHCII+) was observed at the systemic level. Overall, this study illustrates the dynamics of local and systemic inflammatory and immune cell responses associated with intradiscal therapies, which will contribute to designing more successful immunomodulatory treatments for IVD degeneration.

• anti-inflammatory
• biomaterials
• disc degeneration
• inflammation
• nanocomplexes

• Immunomodulation
• Intervertebral disc
• Low back pain
• Macrophages
• Spine

• Humans
• Inflammation/diagnostic imaging
• Inflammation/epidemiology
• Inflammation/immunology
• Intervertebral Disc Degeneration/diagnostic imaging
• Intervertebral Disc Degeneration/epidemiology
• Intervertebral Disc Degeneration/immunology
• Intervertebral Disc Displacement/diagnostic imaging
• Intervertebral Disc Displacement/epidemiology
• Intervertebral Disc Displacement/immunology
• Low Back Pain/diagnostic imaging
• Low Back Pain/epidemiology
• Low Back Pain/immunology
• Lumbar Vertebrae/diagnostic imaging
• Lumbar Vertebrae/immunology
• Remission, Spontaneous

• Fundação para a Ciência e a Tecnologia
• N2020
• COMPETE 2020

• T2 relaxation time
• disc height index
• intervertebral
• magnetic resonance imaging
• small animal model

This study aimed to determine the best size needle to use in inducing IVDD and to find the proper time point of disc degeneration suitable for further biologic treatment study.

First, rat tail level 5/6, 7/8, and 9/10 discs were punctured by 18G, 21G, or 25G needles. Then, degeneration was assessed by radiography, MRI, and histological evaluation at 2, 4, and 6 weeks after puncture. Later, real-time reverse transcriptase (RT-PCR) was used to examine mRNA expressions of aggrecan, collagen type II, hypoxia-inducible factor-1α (HIF-1α), glucose transporter1 (GLUT-1), and vascular endothelial growth factor (VEGF).

Significant differences were identified in almost all parameters compared with the control group in the 18G and 21G group at almost all time points. To assess the effect of different needle sizes on DHI, we used magnetic resonance imaging (MRI), grade, and mRNA expression. We found significant differences between different groups, except for DHI between the 21G group and 25G group and MRI grade between the 18G and 21G group at the 2-week time point. In assessing the effect of different needle sizes on HE staining score and toluidine blue staining grade, statistical differences were observed at some time points. The effects of time on all parameters were significant at almost all time points in all groups.

The middle-size needle (21G) performed better in inducing disc degeneration. The 2-week time point may be better for use in further experimental studies.

• animal model
• coccygeal
• degeneration
• intervertebral disc
• needle puncture

• Hippo pathway
• LATS
• YAP
• intervertebral disc degeneration
• nucleus pulposus

Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed. Disc height index and histological grading score indicated less degeneration for the MSC‐transplanted group, with no significant changes in extracellular matrix composition. Remarkably, MSC transplantation resulted in local downregulation of the hypoxia responsive GLUT‐1 and in significantly less herniation, with higher amounts of Pax5+ B lymphocytes and no alterations in CD68+ macrophages within the hernia. The systemic immune response was analyzed in the blood, draining lymph nodes, and spleen by flow cytometry and in the plasma by cytokine array. Results suggest an immunoregulatory effect in the MSC‐transplanted animals compared with control groups, with an increase in MHC class II+ and CD4+ cells, and also upregulation of the cytokines IL‐2, IL‐4, IL‐6, and IL‐10, and downregulation of the cytokines IL‐13 and TNF‐α. Overall, our results indicate a beneficial effect of systemically transplanted MSCs on in situ IVD regeneration and highlight the complex interplay between stromal cells and cells of the immune system in achieving successful tissue regeneration. Stem Cells Translational Medicine2017;6:1029–1039

• Cell therapy
• Herniation
• Immunomodulation
• Intravenous transplantation
• Paracrine

• Animals
• Bone Marrow Cells/cytology
• Cells, Cultured
• Intervertebral Disc/cytology
• Male
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/cytology
• Mesenchymal Stem Cells/physiology
• Rats
• Regeneration/physiology