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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

Abstract Background Intradiscal condoliase injection is an alternative therapeutic option for lumbar disc herniation (LDH). However, it is often associated with disc degeneration. Several in vivo studies have demonstrated the regenerative potential of platelet-rich plasma (PRP) in disc degeneration. Thus, we hypothesized that the intradiscal injection of PRP releasate (PRPr), a soluble releasate isolated from PRP, has the potential to regenerate degenerated intervertebral discs (IVDs) induced by condoliase. This study examined the regenerative effects of PRPr on rabbit IVDs degenerated following condoliase injection. Methods Eleven New Zealand white rabbits were used in this study. Condoliase (12.5 mU/10 μl) was injected into two non-contiguous discs (L2-L3 and L4-L5), and L3-L4 disc was left intact as a non-injection control. Saline (20 μl) or PRPr (20 μl) was randomly injected into L2-L3 and L4-L5 discs 4 weeks after the condoliase injection. Disc height (DH) was radiographically monitored biweekly from the day of condoliase injection to 16 weeks post-injection. Changes in DH were expressed as percentage DH (%DH) normalized to the baseline DH. Sixteen weeks after condoliase injection, all rabbits were euthanized, and subjected to MRI and histological analyses. Results Intradiscal injection of condoliase induced a significant decrease in %DH (L2-L3 and L4-L5) to 52.0% at week 4. However, the %DH began to return to normal after saline injection and reached 76.3% at week 16. In the PRPr group, %DH began to recover to normal after the PRPr injection and was restored to 95.5% at week 16. The MRI-modified Pfirrmann grade of the PRPr group was significantly lower than that of the saline group (P

Study Design Retrospective study. Purpose This study aimed to evaluate the incidence, characteristics, and risk factors for clinical L5–S1 adjacent segment degeneration (ASD) after L5 floating lumbar fusion. Overview of Literature ASD is known to occur after lumbar spine fusion at a certain frequency. Several studies on radiological L5–S1 ASD have been reported. However, there are only a few studies on L5–S1 ASD with clinical symptoms, including back pain and/or radiculopathy. Methods In total, 306 patients who received L5 floating lumbar fusion were included in this study. Clinical L5–S1 ASD was defined as newly developed radiculopathy in relation to the L5–S1 segment. Patients’ medical records and imaging data were retrospectively analyzed. The risk factors for clinical ASD were assessed by an inverse probability of treatment weighting-adjusted logistic regression analysis. Results Clinical L5–S1 ASD occurred in 17 patients (5.6%). The mean onset time of L5–S1 ASD was 12.9±7.5 months after the primary surgery. Among these patients, 10 (58.8%) presented with clinical L5–S1 ASD within 12 months. Reoperation was performed in three patients (1.0%). The severity of L5–S1 disk degeneration did not affect the occurrence of L5–S1 ASD. Logistic regression analysis showed that the number of fusion levels was a significant risk factor for clinical L5–S1 ASD. Conclusions The incidence and characteristics of clinical L5–S1 ASD after L5 floating lumbar fusion were retrospectively investigated. This study established that the number of fusion levels was a significant candidate factor for clinical L5–S1 ASD. Careful clinical follow-up is deemed necessary after L5 floating lumbar fusion surgery, especially for patients who received multiple-level fusions.

Glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs) contribute to the sensitization of primary afferents and are involved in the pathogenesis of inflammatory pain. The purpose of this preliminary study was to examine the expression of other GFLs (neurturin (NRTN), artemin (ARTN), persephin (PSPN)) and receptors in human IVD cells and tissues exhibiting early and advanced stages of degeneration. Human IVD cells were cultured as a monolayer after isolation from the nucleus pulposus (NP) and anulus fibrosus (AF) tissues. The mRNA expression of NRTN, ARTN, PSPN, and their receptors (GFRA2–GFRA4) was quantified using real-time PCR. Protein expression was evaluated using immunohistochemistry and Western blotting. The expression of NRTN, ARTN, PSPN, and their co-receptors (GFRA2-GFRA4) was identified in human IVD cells at both mRNA and protein levels. A trend was noted wherein the mRNA expression of ARTN, PSPN, and GFRA2 was upregulated by IL-1β treatment in a dose-dependent manner. The percentages of immunopositive cells in the advanced degenerate stage of ARTN, PSPN, and GFRA2 were significantly higher than those in the early degenerate stage. Their expression was enhanced in advanced tissue degeneration, which suggests that GFLs (ARTN and PSPN) may be involved in the pathogenesis of discogenic pain.

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.

Abstract Background Establishing an optimal animal model for intervertebral disc (IVD) degeneration is essential for developing new IVD therapies. The intra-articular injection of monosodium iodoacetate (MIA), which is commonly used in animal models of osteoarthritis, induces cartilage degeneration and progressive arthritis in a dose- and time-dependent manner. The purpose of this study was to determine the effect of MIA injections into rabbit IVDs on the progression of IVD degeneration evaluated by radiographic, micro-computerized tomography (micro-CT), magnetic resonance imaging (MRI), and histological analyses. Methods In total, 24 New Zealand White (NZW) rabbits were used in this study. Under general anesthesia, lumbar discs from L1–L2 to L4–L5 had a posterolateral percutaneous injection of MIA in contrast agent (CA) (L1–L2: CA only; L2–L3: MIA 0.01 mg; L3–L4: 0.1 mg; L4–L5: 1.0 mg; L5–L6: non-injection (NI) control). Disc height was radiographically monitored biweekly until 12 weeks after injection. Six rabbits were sacrificed at 2, 4, 8, and 12 weeks post-injection and processed for micro-CT, MRI (T2-mapping), and histological analyses. Three-dimensional (3D) disc height in five anatomical zones was evaluated by 3D reconstruction of micro-CT data. Results Disc height of MIA-injected discs (L2–L3 to L4–L5) gradually decreased time-dependently (P < 0.0001). The disc height of MIA 0.01 mg-injected discs was significantly higher than those of MIA 0.1 and 1.0 mg-injected discs (P < 0.01, respectively). 3D micro-CT analysis showed the dose- and time-dependent decrease of 3D disc height of MIA-injected discs predominantly in the posterior annulus fibrosus (AF) zone. MRI T2 values of MIA 0.1 and 1.0 mg-injected discs were significantly decreased compared to those of CA and/or NI controls (P < 0.05). Histological analyses showed progressive time- and dose-degenerative changes in the discs injected with MIA (P < 0.01). MIA induced cell death in the rabbit nucleus pulposus with a high percentage, while the percentage of cell clones was low. Conclusions The results of this study showed, for the first time, that the intradiscal injection of MIA induced degenerative changes of rabbit IVDs in a time- and dose-dependent manner. This study suggests that MIA injection into rabbit IVDs could be used as an animal model of IVD degeneration for developing future treatments.

Background and Objectives: Adult (de novo) degenerative scoliosis (ADS) develops through degenerative changes in the lumbar spine, leading to spinal malalignment, which usually progresses with age. Strong evidence for non-operative care in patients with ADS is lacking, and whether physical exercise can improve the scoliosis curve remains unknown. Materials and Methods: We present a case of early stage ADS in which the coronal imbalance was improved by daily training. A 65-year-old female patient complained of lower back pain (LBP) and bilateral leg pain. She was diagnosed with early stage ADS with lumbar degenerative spondylolisthesis by imaging. She completed six months of daily physical training, including swimming, aerobic bikes, stretching, yoga, and Taijiquan. Results: Her LBP and neurological symptoms improved, and coronal–spinal balance was restored, which was maintained for four years by continued daily physical training. Conclusions: This is the first case of a 65-year-old ADS patient whose coronal balance was significantly restored through daily physical training. Substantial physical training focused on trunk muscle strength is important for spinal stabilization and for improving spinal malalignment in patients with early stage ADS.

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.

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.

Marked cellular changes occur in human intervertebral disc (IVD) degeneration during disc degeneration with biochemical changes. Genome-wide analysis of the DNA methylation profile has identified 220 differentially methylated loci associated with human IVD degeneration. Among these, two cell-cycle–associated genes, growth arrest and DNA damage 45 gamma (GADD45G) and cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), were focused on. The expression of GADD45G and CAPRIN1 in human IVDs remains unknown. We aimed to examine the expression of GADD45G and CAPRIN1 in human nucleus pulposus (NP) cells and evaluate those in human NP tissues in the early and advanced stages of degeneration according to Pfirrmann magnetic resonance imaging (MRI) and histological classifications. Human NP cells were cultured as monolayers after isolation from NP tissues by sequential enzyme digestion. Total RNA was isolated, and the mRNA expression of GADD45G and CAPRIN1 was quantified using real-time polymerase chain reaction. To examine the effects of pro-inflammatory cytokines on mRNA expression, human NP cells were cultured in the presence of IL-1β. Protein expression was evaluated using Western blotting and immunohistochemistry. GADD45G and CAPRIN1 expression was identified in human NP cells at both mRNA and protein levels. The percentage of cells immunopositive for GADD45G and CAPRIN1 significantly increased according to the Pfirrmann grade. A significant correlation between the histological degeneration score and the percentage of GADD45G-immunopositive cells was identified, but not with that of CAPRIN1-immunopositive cells. The expression of cell-cycle-associated proteins (GADD45G and CAPRIN1) was enhanced in human NP cells at an advanced stage of degeneration, suggesting that it may be regulated during the progression of IVD degeneration to maintain the integrity of human NP tissues by controlling cell proliferation and apoptosis under epigenetic alteration.

Abstract Background Previous clinical studies reported that thoracolumbar vertebral fractures (VFs) associated with high energy spine trauma cause adjacent intervertebral disc (IVD) degeneration; however, the effect of non-traumatic VFs on the progression of adjacent disc degeneration remains to be determined. The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs. Methods Ninety-eight consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. Five hundred eighty-eight vertebral bodies (from T12 to L5) and 486 discs (from T12/L1 to L4/L5) were analyzed. The degree of IVD degeneration was evaluated by magnetic resonance imaging (MRI) and classified into two groups according to Pfirrmann’s classification. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed. Results IVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P

PurposeLumbar radiography is a primary screening tool for lumbar spondylosis (LS). Kellgren-Lawrence (KL) classification is widely used to evaluate LS; however, it cannot individually evaluate each radiographic feature. The purpose of this study was to 1) evaluate radiographic LS using a novel elemental grading system and 2) investigate the relationship between the grades of radiographic LS and low back pain (LBP) in a population-based cohort study.MethodsA total of 260 (75 men, 185 women; mean age, 71.5 ± 8.7 years) participants were included in this study. Participants were divided into two groups according to the presence of LBP (LBP- and LBP+ groups). Radiographic features, including osteophyte (OP), disc height narrowing (DHN), vertebral sclerosis (VS), and spondylolisthesis (SL), were classified between grades of 0-2 grades according to the extent of radiographic changes. The sum of grades at each intervertebral level was designated as the intervertebral grade (IG).ResultsIntra- and inter-observer reliability (kappa coefficient) of OP, DHN, VS, and SL were 0.82-0.92. OP, DHN, VS, and IG grades were significantly higher in the LBP+ group than in the LBP- group. There were no significant differences in KL grades between the LBP- and LBP+ groups. Logistic regression analysis demonstrated that VS grade was a significant independent factor associated with LBP.ConclusionThe novel elemental grading system of LS would reflect LBP more accurately than the KL classification by individually evaluating each radiographic feature.

Abstract Background The endplate-intervertebral disc (IVD) complex is closely interrelated with the vertebral body (VB) in the structural integrity of the anterior spinal column, including biomechanical and biological functions. Endplate and IVD injuries are usually found in association with vertebral fractures (VFs); however, little is known about their relevance to the healing of osteoporotic VFs (OVFs). The first purpose of this study was to evaluate the incidence and occurrence pattern of endplate and IVD injuries associated with single- and acute-OVFs, and the second was to evaluate the influence of endplate and IVD injuries on the occurrence of delayed union. Methods Endplate and IVD injuries associated with single- and acute-OVFs were retrospectively evaluated using magnetic resonance imaging (MRI). Vertebrae of 168 patients were included in the study. The occurrence rate and type of endplate and IVD injuries were radiologically evaluated, and the association between endplate and IVD injuries was statistically analyzed. Vertebrae of 85 patients, who received conservative treatment for acute OVFs, were included in the study and classified into two groups, union and delayed union, at 6 months after injury. To identify factors predicting delayed union, uni- and multivariate statistical analyses were performed. Vertebral MRI signal alternation patterns and endplate and IVD injuries were included as candidate factors in the logistic model. Results In association with OVFs, endplate injuries were observed in 103 of the 168 vertebrae (61%), and IVDs lesions were observed in 101 of 168 OVFs (60%); the occurrence of both injuries was significantly associated. Although no significant association with endplate and IVD injuries was identified, multivariate analysis demonstrated that intravertebral signal alternation (focal high signal intensity) and posterior wall injury were independent risk factors that predicted delayed union. Conclusions The results of this study showed that endplate and IVD injuries were found in approximately 60% of single and acute OVFs. These results suggest that fracture healing of OVFs would be mainly attributed to vertebral factors, including mechanical stress and metabolic status, among the three components of the anterior spinal column.

Abstract Background The expression of the receptor activator of nuclear factor kappa B (RANK) /RANK ligand (RANKL) /osteoprotegerin (OPG) system and its association with the progression of intervertebral disc (IVD) degeneration has recently been reported in a human IVD. However, the effect of the RANK/RANKL/OPG system on the matrix metabolism of human IVD cells, especially on the expression of catabolic factors relevant to IVD degeneration, remains unknown. The purpose of this study was to examine the expression of the RANK/RANKL/OPG system, and then to evaluate the effect of this system on the expression of catabolic factors by human IVD cells. Methods Annulus fibrosus (AF) and nucleus pulposus (NP) cells isolated by sequential enzyme digestion from human IVD tissues obtained during spine surgeries were monolayer cultured. The expression of the RANK/RANKL/OPG system was determined using immunohistochemical methods and real-time polymerase chain reaction (PCR). To evaluate the influence of interleukin-1 beta (IL-1β) stimulation on the mRNA expression of RANK, RANKL, and OPG, recombinant human IL-1β (rhIL-1β) was administered in the culture media of IVD cells. To examine the influence of RANKL signaling on the expression of matrix metalloprotease-3 (MMP-3), MMP-13, and IL-1β, the cells were cultured with exogenous recombinant human RANKL (rhRANKL), recombinant human OPG (rhOPG) or anti-human RANKL mouse monoclonal antibody (ahRANKL-mAB) with or without rhIL-1β. Results Immunoreactivity to RANK/RANKL/OPG and the mRNA expression of the three genes were obviously identified in both AF and NP cells. rhIL-1β stimulation significantly upregulated the mRNA expression level of RANK/RANKL/OPG. The mRNA expression of catabolic factors was significantly upregulated by stimulation of rhRANKL in the presence of rhIL-1β. On the other hand, the administration of either rhOPG or ahRANKL-mAB significantly suppressed the mRNA expression of catabolic factors that had been upregulated by rhIL-1β stimulation. The suppressive effect of ahRANKL-mAB against rhIL-1β stimulation was also confirmed by the protein expression of MMP-3. Conclusions The present study showed that the RANK/RANKL/OPG system may be involved in the progression of IVD degeneration. This study also suggested the potential use of anti-RANKL monoclonal antibody and OPG as therapeutic agents to suppress the progression of IVD degeneration.

With improving prognosis for recipients of liver transplantation, the necessity of medical care for musculoskeletal disorders, including spinal diseases, of these patients is also increasing. Only a few reports are available on cases of spine surgery following liver transplantation. Furthermore, a case of lateral access surgery following liver transplantation has not thus far been reported. The purpose of this study is to present the first two cases of patients treated with lateral access spine surgery following liver transplantation. Case 1. A 49-year-old female had received living donor liver transplantation (LT) for acute-on-chronic liver failure (ACLF) ten years prior to spine surgery. The patient underwent two levels of lateral lumbar interbody fusion (LLIF) followed by posterior lumbar interbody fusion (PLIF) for degenerative lumbar disease. Although neurological symptoms in the lower extremity improved, a liver disorder resulting from acetaminophen-induced hepatotoxicity occurred at an early stage following spine surgery. Case 2. A 66-year-old female had received living donor liver transplantation for hepatocellular carcinoma (HCC) six years prior to spine surgery. She underwent posterior instrumentation surgery followed by a T12 corpectomy using a wide-foot print expandable cage for T12 vertebral collapse. Following surgery, her weakened muscle strength in the lower extremities was significantly improved. Lateral access spine surgery for lumbar and thoracolumbar lesions can be successfully performed for patients following liver transplantation. However, careful follow-up should be performed for complications related to the function of the liver graft following spine surgery.

Background and Objectives: Clinical studies of platelet-rich plasma (PRP) for the treatment of low back pain (LBP) have been reported; however, less is known about its long-term efficiency. Materials and Methods: This study was a long-term follow-up of a previous prospective clinical feasibility study for the use of PRP releasate (PRPr) to treat discogenic LBP patients. Among 14 patients, 11 patients were evaluated for a long-term survey. The efficacy was assessed by a visual analogue scale (VAS) for LBP intensity and the Roland-Morris Disability Questionnaire (RDQ) for LBP-related disability. Radiographic disc height was evaluated for seven patients. Results: Improvements in VAS and RDQ were sustained at an average of 5.9 years after the intradiscal injection of PRPr (p < 0.01 vs. baseline, respectively). Clinically meaningful improvements (more than 30% decrease from baseline) in VAS and RDQ were identified in 91% of patients at final survey. The radiographic measurement of disc height of PRPr-injected discs showed a mild decrease (13.8% decrease compared to baseline) during the average 5.9 years. Conclusions: The results of this study with a small number of patients suggest that the intradiscal injection of PRPr has a safe and efficacious effect on LBP improvement for more than 5 years after treatment. Further large-scale studies would be needed to confirm the clinical evidence for the use of PRPr for the treatment of patients with discogenic LBP.

Abstract Background The degeneration of the intervertebral disc (IVD) is characterized by proteolytic degradation of the extracellular matrix, and its repair requires the production of an extracellular matrix with a high proteoglycan-to-collagen ratio characteristic of a nucleus pulposus (NP)-like phenotype in vivo. At the moment, there is no medical treatment to reverse or even retard disc degeneration. The purpose of the present study was to determine if a low dose of short link N (sLN), a recently discovered fragment of the link N peptide, could behave in a manner similar to that of link N in restoring the proteoglycan content and proteoglycan-to-collagen ratio of the disc in a rabbit model of IVD degeneration, as an indication of its potential therapeutic benefit in reversing disc degeneration. Methods Adolescent New Zealand white rabbits received an annular puncture with an 18-gauge needle into two noncontiguous discs to induce disc degeneration. Two weeks later, either saline (10 μL) or sLN (25 μg in 10 μL saline) was injected into the center of the NP. The sLN concentration was empirically chosen at a lower molar concentration equivalent to half that of link N (100 μg in 10 μL). The effect on radiographic, biochemical and histologic changes were evaluated. Results Following needle puncture, disc height decreased by about 25–30% within 2 weeks and maintained this loss for the duration of the 12-week study; a single 25-μg sLN injection at 2 weeks partially restored this loss in disc height. sLN injection led to an increase in glycosaminoglycans (GAG) content 12 weeks post-injection in both the NP and annulus fibrosus (AF). There was a trend towards maintaining control disc collagen-content with sLN supplementation and the GAG-to-collagen ratio in the NP was increased when compared to the saline group. Conclusions When administered to the degenerative disc in vivo, sLN injection leads to an increase in proteoglycan content and a trend towards maintaining control disc collagen content in both the NP and AF. This is similar to link N when it is administered to the degenerative disc. Thus, pharmacologically, sLN supplementation could be a novel therapeutic approach for treating disc degeneration.

Abstract Background 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.

Study DesignPreliminary clinical trial.PurposeTo determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain.Overview of LiteraturePRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism.MethodsInclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification).ResultsData were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p

The behaviors performed on the nest by the foundress queen and workers of the paper wasp Polistes jokahamae were observed in three colonies in the field and one colony in a cage set in the field. Each queen was rarely ranked top in the dominance hierarchy determined by the pairwise dominance–subordinate interactions and did not display more frequent direct aggression toward the top-ranked worker than toward other workers. Furthermore, the queen exhibited aggression less frequently than did the most aggressive workers in all four colonies. The dominance order among the workers was positively correlated with the emergence order, with older workers being more dominant. The queen laid eggs in a dominant or monopolized way; some dominant workers laid eggs in three colonies. These observations suggest that the queen maintained her queen status, including her reproductive priority, using signals rather than aggression. Lateral vibrations (rapidly laterally vibrating the abdomen) and abdominal rubbing (rubbing the abdomen onto the comb) appeared to be candidate signals of the fertility or reproductive potential of the performer. Lateral vibrations were performed only by the queen, and their frequency was positively correlated with the frequency of ovipositing. The queen and some dominant workers performed abdominal rubbing; the frequency was higher for the queen than for any of the dominant workers early in the colony’s development, but not later. Although performers of abdominal rubbing were more likely to lay eggs than non-performers, the frequency of abdominal rubbing was not a predictor of the frequency of ovipositing.

Purpose: The purpose of this study was to evaluate prospectively the clinical effectiveness of immediate loading of implants with complete-arch fixed prostheses in edentulous maxillae after the implants were placed with flapless guided surgery. Materials and Methods: Patients with edentulous maxillae who visited a single dental clinic during the recruitment period (April 2011 to May 2012) were selected by consecutive sampling and predetermined selection criteria. Four to six implants were placed in each patient with flapless guided surgery. The outcome measures were insertion torque, surgical time, postoperative pain (100-mm visual analog scale), marginal bone level change, implant survival, and oral health–related quality of life. Patients were followed for up to 1 year. Results: Fifty patients received 290 implants. All implants were immediately loaded 2 hours after placement with prefabricated fixed provisional prostheses. Two patients dropped out of the study. Hence, analyses were conducted for 278 implants in 48 patients (26 men, 22 women; mean age 56.0 ± 8.3 years; age range, 34 to 74 years). The average insertion torque was 57.7 ± 16.6 Ncm, the average surgical time was 22.9 ± 4.7 minutes, and the average score for postoperative pain was 14.7 ± 9.3. One year after immediate loading, the implant survival rate was 98.6%. Four implants showed mobility early after implant placement and were lost. Mean marginal bone level changes were –0.32 ± 0.43 mm. Scores on the Oral Health Impact Profile-54 (Japanese version) improved significantly after prosthetic treatment. Conclusion: The results of this study indicate that this treatment method for edentulous maxillae is predictable, with a high implant survival rate and a clinically reasonable improvement in oral health–related quality of life. [ABSTRACT FROM AUTHOR]