RANK/RANKL/OPG system in the intervertebral disc

application/pdf内容の要旨・審査結果の要旨 / 三重大学大学院医学系研究科 生命医科学専攻 病態修復医学講座 運動器外科学分

RANK/RANKL/OPG system in the intervertebral disc

application/pdfBackground: The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the function of RANKL in the matrix metabolism of the rat IVD. Methods: Sprague-Dawley, 12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected thoracolumbar discs were monolayer-cultured. RANK/ RANKL/OPG expression in rat IVDs was examined using real-time polymerase chain reaction (PCR) and immunohistochemical analysis (cultured cells and IVD tissues). To examine the effect of interleukin-1β (IL-1β) stimulation on the mRNA levels of RANK, RANKL and OPG, the cells were cultured with or without recombinant human IL-1β (rhIL-1β). To evaluate the effect of RANKL on the mRNA expression of catabolic factors (IL-1β, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were cultured with RANKL in the presence or absence of rhIL-1β. The immunohistochemical expression of this system was also evaluated using human IVD tissues with different grades of degeneration. Results: mRNA expression levels of RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes and/or cytoplasm of the three types of cells. The mRNA level of RANKL was significantly upregulated by treatment with rhIL-1β of the three types of cells. Treatment with RANKL without rhIL-1β did not induce significant effects on the mRNA expression of catabolic factors by AF, NP and CEP cells. However, the expression was significantly upregulated by stimulation with RANKL in the presence of rhIL-1β. There was a general trend for more RANK/RANKL/OPG-positive cells in human IVD tissues in an advanced stage of degeneration compared to an early stage. Conclusions: Our study showed the possibility that the RANK/RANKL/OPG system may play a part in the process of intervertebral disc degeneration.本文 / Department of Orthopaedic Surgery, Mie University Graduate School of Medicine10

Retrospective Analysis of Factors Associated with the Treatment Outcomes of Intradiscal Platelet-Rich Plasma-Releasate Injection Therapy for Patients with Discogenic Low Back Pain

Background and Objectives: Recently, the clinical application of platelet-rich plasma (PRP) has gained popularity for the treatment of degenerative disc diseases. However, the regenerative effects and factors associated with treatment outcomes after intradiscal injection of PRP remain unknown. This study aimed to evaluate time-dependent changes in imaging findings related to intervertebral disc (IVD) degeneration and to identify factors associated with the outcomes of PRP injection therapy. Materials and Methods: A retrospective analysis of a previous randomized clinical trial of intradiscal injection of the releasate isolated from PRP (PRPr) in patients with discogenic low back pain (LBP) was performed. Radiographic parameters (segmental angulation and lumbar lordosis) and MRI phenotypes, including Modic changes, disc bulge, and high-intensity zones (HIZs), were evaluated at baseline and 6 and 12 months post-injection. Treatment outcomes were evaluated based on the degree of LBP and LBP-related disability at 12 months post-injection. Results: A total of 15 patients (mean age: 33.9 ± 9.5 years) were included in this study. Radiographic parameters showed no significant changes after the PRPr injection. There were no remarkable changes in the prevalence or type of MRI phenotype. Treatment outcomes were significantly improved after treatment; however, the number of targeted discs and the presence of posterior HIZs at baseline were significantly but negatively associated with treatment outcomes. Conclusions: Intradiscal injection of PRPr significantly improved LBP and LBP-related disability 12 months post-injection; however, patients with multiple target lesions or posterior HIZs at baseline were significantly associated with poor treatment outcomes

Progression of vertebral deformity of prevalent vertebral fractures in the elderly: a population-based study

Abstract Background Little is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study. Methods A total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression. Results The progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities. Conclusion This study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities

Localization diagnosis of low back pain in a population-based study of a Japanese mountain village

Purpose The purposes of this study were to investigate 1) the location of low back pain (LBP) and 2) the relationships between the location of LBP and the LBP intensity or the quality of life (QoL) in a population-based study. Methods The location of LBP was categorized into four areas using palpation: midline of the lumbar region, paravertebral muscles, upper buttock, and sacroiliac joint. The extent of LBP in the situations/positions was assessed. The relationships between the location of LBP and the extent of LBP on the QoL were statistically analyzed. Results 174 participants (average age: 72.3 years-old) were analyzed in this study. 93 participants (53.4% of the total) who had experienced LBP in the past three months were included in the LBP-positive group. Numerical rating scale (NRS) scores of the LBP-positive group were highest in the standing position. 51.6% of the LBP-positive group had LBP at the midline of the lumbar region, 40.9% at the paravertebral muscles, 28.0% at the upper buttock, and 15.1% at the sacroiliac joint. In the standing position, NRS scores of LBP at the upper buttock were significantly higher than those at the midline of the lumbar region and the paravertebral muscles (PConclusion Our study was the first report to investigate the location of LBP using palpation in a population-based study. LBP localization was significantly associated with LBP intensity and LBP-related QoL

Localization diagnosis of low back pain in a population-based study of a Japanese mountain village.

PurposeThe purposes of this study were to investigate 1) the location of low back pain (LBP) and 2) the relationships between the location of LBP and the LBP intensity or the quality of life (QoL) in a population-based study.MethodsThe location of LBP was categorized into four areas using palpation: midline of the lumbar region, paravertebral muscles, upper buttock, and sacroiliac joint. The extent of LBP in the situations/positions was assessed. The relationships between the location of LBP and the extent of LBP on the QoL were statistically analyzed.Results174 participants (average age: 72.3 years-old) were analyzed in this study. 93 participants (53.4% of the total) who had experienced LBP in the past three months were included in the LBP-positive group. Numerical rating scale (NRS) scores of the LBP-positive group were highest in the standing position. 51.6% of the LBP-positive group had LBP at the midline of the lumbar region, 40.9% at the paravertebral muscles, 28.0% at the upper buttock, and 15.1% at the sacroiliac joint. In the standing position, NRS scores of LBP at the upper buttock were significantly higher than those at the midline of the lumbar region and the paravertebral muscles (PConclusionOur study was the first report to investigate the location of LBP using palpation in a population-based study. LBP localization was significantly associated with LBP intensity and LBP-related QoL

Morphology of intervertebral disc ruptures evaluated by vacuum phenomenon using multi-detector computed tomography: association with lumbar disc degeneration and canal stenosis

Abstract Background The progression of intervertebral disc (IVD) degeneration leads to rupture within IVD tissues. The location and appearance of areas of gaseous radiolucency in the IVD, known as vacuum phenomena (VPs), are considered to indirectly indicate the position and extent of IVD rupture. The clinical significance of VPs in degenerated IVDs is not fully understood. The purpose of this study is to assess and classify the morphology of IVD ruptures by the presence of intradiscal VPs, and to examine the association between morphological VP-positive IVD ruptures and degenerative lumbar diseases. Methods IVD rupture was evaluated by the presence of VPs using computed tomography (CT) imaging. VP shape (spot, linear, island) was classified using sagittal imaging, and VP distribution (A-N: anterior AF-NP; N: NP only; N-P: NP-posterior AF; A-N-P: anterior and posterior AF-NP) was classified using axial imaging. The disc height index (DHI) was calculated from lateral radiographs. Disc degeneration and lumbar spinal stenosis were evaluated by MRI grade. Results In the VP shape analysis, the island type was the most common, followed by linear and spot types. In the VP distribution analysis, A-N was the most common group, followed by N, N-P and A-N-P. Intra- and inter-observer reliabilities were statistically sufficient to classify different rupture shapes and distributions. The DHI tended to be lower in discs that contained VPs, especially in the anterior AF area. The shape and distribution of intradiscal VPs were significantly associated with the degree of disc degeneration and lumbar spinal stenosis graded by MRI. Discs with VPs extending from the NP into the anterior and/or posterior AF had a significantly higher proportion of advanced disc degeneration (Pfirrmann’s classification: grades IV and V). Conclusions This is the first study to analyze the morphology of IVD rupture evaluated by the presence of intradiscal VPs using CT imaging. This classification can comprehensively present the shape and axial distribution of VPs within IVDs. Intradiscal VPs are associated with the progression of disc degeneration and lumbar spinal stenosis

Advances in Platelet-Rich Plasma Treatment for Spinal Diseases: A Systematic Review

Spinal diseases are commonly associated with pain and neurological symptoms, which negatively impact patients’ quality of life. Platelet-rich plasma (PRP) is an autologous source of multiple growth factors and cytokines, with the potential to promote tissue regeneration. Recently, PRP has been widely used for the treatment of musculoskeletal diseases, including spinal diseases, in clinics. Given the increasing popularity of PRP therapy, this article examines the current literature for basic research and emerging clinical applications of this therapy for treating spinal diseases. First, we review in vitro and in vivo studies, evaluating the potential of PRP in repairing intervertebral disc degeneration, promoting bone union in spinal fusion surgeries, and aiding in neurological recovery from spinal cord injury. Second, we address the clinical applications of PRP in treating degenerative spinal disease, including its analgesic effect on low back pain and radicular pain, as well as accelerating bone union during spinal fusion surgery. Basic research demonstrates the promising regenerative potential of PRP, and clinical studies have reported on the safety and efficacy of PRP therapy for treating several spinal diseases. Nevertheless, further high-quality randomized controlled trials would be required to establish clinical evidence of PRP therapy