• Bioactive therapies
• Degenerative disc disease
• Intervertebral disc degeneration
• Nucleus pulposus replacement
• Regenerative medicine
• Stem cell therapy

• Humans
• Intervertebral Disc Degeneration/therapy
• Regenerative Medicine/methods
• Genetic Therapy/methods
• Intervertebral Disc/pathology
• Animals
• Cell- and Tissue-Based Therapy/methods
• Drug Delivery Systems

• 3D culture
• cell viability
• intervertebral disc
• qPCR
• sulfation alginate

• #955735 H2020 Marie Skłodowska Curie International Training Network (ITN) "disc4all"

• Apoptosis
• degeneration
• disc herniation
• immunohistochemical
• microdiscectomy

• culture systems
• regenerative medicine
• stem cell

• I01 RX002274 RRD VA
• I21 RX003447 RRD VA
• IK6 RX003416 RRD VA
• Department of Veterans Affairs

• IGF-1
• mechanical loading
• migration
• muscle secretome
• proliferation
• tenocyte

• Receptor, IGF Type 1
• Insulin-Like Growth Factor I
• Tenocytes
• Secretome
• Myoblasts
• Cell Proliferation

• exosome
• intervertebral disc degeneration
• small molecule
• stem cell
• therapy

• Humans
• Intervertebral Disc Degeneration/surgery
• Quality of Life
• Intervertebral Disc
• Low Back Pain/etiology
• Low Back Pain/therapy
• Aging

• R15 HD099588 NICHD NIH HHS

• Brain
• Extracellular vesicles
• Growth factors
• Neuroprotection
• Neurorestoration
• Platelet neurotrophins

• Brain/metabolism
• Humans
• Neurodegenerative Diseases/drug therapy
• Neurodegenerative Diseases/metabolism
• Neuroprotection
• Neuroprotective Agents/metabolism
• Neuroprotective Agents/therapeutic use
• Parkinson Disease/metabolism

• 108-3805-005-111 Taipei Medical University
• 107-2314-B-038 Ministry of Science and Technology, Taiwan
• 110-2314-B-038-079 Ministry of Science and Technology, Taiwan
• 108-2911-I-038-503 Ministry of Science and Technology, Taiwan
• DP2-107-21121-01N 09 Ministry of Education

Low back pain (LBP) is a common musculoskeletal symptom, which brings a lot of pain and economic loss to patients. One of the most common causes of LBP is intervertebral disc degeneration (IVDD). However, pathogenesis is still debated, and therapeutic options are limited. Insulin-like growth factor (IGF) signaling pathways play an important role in regulating different cell processes, including proliferation, differentiation, migration, or cell death, which are critical to the homeostasis of tissues and organs. The IGF signaling is crucial in the occurrence and progression of IVDD. The activation of IGF signaling retards IVDD by increasing cell proliferation, promoting extracellular matrix (ECM) synthesis, inhibiting ECM decomposition, and preventing apoptosis and senescence of disc cells. However, abnormal activation of IGF signaling may promote the process of IVDD. IGF signaling is currently considered to have a promising treatment prospect for IVDD. An in-depth understanding of the role of IGF signaling in IVDD may help find a novel approach for IVDD treatment.

• degeneration
• insulin-like growth factor
• intervertebral disc
• low back pain
• nucleus pulposus

Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.

• PDGF-BB
• degeneration
• extracellular matrix
• intervertebral disc
• pyroptosis

Associated with abnormal angiogenesis and disc dysfunction, lumbar disc degeneration (LDD) appears to be an important disease suffered by elderly people. Previous studies have highlighted the importance of insufficient insulin-like growth factor 1 (IGF1) and excessive vascular endothelial growth factor (VEGF) in the development and progression of LDD, though a practical therapeutic strategy is lacking.

The expression of IGF1 and VEGF was assessed in LDD specimens compared to normal disc tissue as a control. A gene therapy approach was performed, in which an adeno-associated virus (AAV) carrying both IGF1 and shVEGF (AAV-IGF1/shVEGF) was orthotopically injected to the rats that had undergone LDD. The alterations in IGF1 and VEGF levels in the treated disc tissue were confirmed by immunohistochemistry. The outcome of this therapy was assessed by disc cell death using an annexin V-FITC assay and by assessing lumbar proteoglycan and collagen II levels using ELISA.

IGF1 expression was significantly downregulated in LDD, while VEGF expression was significantly upregulated in LDD, compared to normal controls. Combined AAV-IGF1/shVEGF treatment simultaneously corrected the insufficient IGF1 and the excessive VEGF in LDD rats. Moreover, AAV-IGF1/shVEGF significantly reduced disc cell death in the vertebral pulp and annulus fibrosus and significantly enhanced the lumbar proteoglycan and collagen II levels.

The simultaneous increase in IGF1 and depletion of VEGF effectively prevented the development of LDD, suggesting its potential as a novel therapeutic approach for LDD which is clinically translatable.

• Lumbar disc degeneration (LDD)
• adeno-associated virus (AAV)
• gene therapy
• insulin-like growth factor 1 (IGF1)
• vascular endothelial growth factor (VEGF)

• Biology
• biological transformations
• degenerative disc disease
• growth factors
• mitochondria
• prostate gland
• seminal secretions.

• death receptor pathway
• endoplasmic reticulum stress pathway
• intervertebral disc degeneration
• mitochondrial pathway
• targeted therapy

Leptin—the most famous adipose tissue-secreted hormone—in the human body is mostly observed in a negative connotation, as the hormone level increases with the accumulation of body fat. Nowadays, fatness is becoming another normal body shape. Fatness is burdened with numerous illnesses—including low back pain and degenerative disease of lumbar intervertebral disc (IVD). IVD degeneration and IVD inflammation are two indiscerptible phenomena. Irrespective of the underlying pathophysiological background (trauma, obesity, nutrient deficiency), the inflammation is crucial in triggering IVD degeneration. Leptin is usually depicted as a proinflammatory adipokine. Many studies aimed at explaining the role of leptin in IVD degeneration, though mostly in in vitro and on animal models, confirmed leptin’s “bad reputation”. However, several studies found that leptin might have protective role in IVD metabolism. This review examines the current literature on the metabolic role of different depots of adipose tissue, with focus on leptin, in pathogenesis of IVD degeneration.

• inflammation
• intervertebral disc
• leptin
• low back pain
• obesity

• Herniated disc
• Inflammation
• Intervertebral disc
• MRI severity
• Pain

Inflammation plays an essential role in the development of lumbar disc degeneration (LDD), although the exact effects of macrophage subtypes on LDD remain unclear. Based on previous studies, we hypothesized that M2-polarization of local macrophages and simultaneous suppression of their production of fibrotic transforming growth factor beta 1 (TGFβ1) could inhibit progression of LDD. Thus, we applied an orthotopic injection of adeno-associated virus (AAV) carrying shRNA for DNA Methyltransferase 1 (DNMT1) and/or shRNA for TGFβ1 under a macrophage-specific CD68 promoter to specifically target local macrophages in a mouse model for LDD. We found that shDNMT1 significantly reduced levels of the pro-inflammatory cytokines TNFα, IL-1β and IL-6, significantly increased levels of the anti-inflammatory cytokines IL-4 and IL-10, significantly increased M2 macrophage polarization, significantly reduced cell apoptosis in the disc degeneration zone and significantly reduced LDD-associated pain. The anti-apoptotic and anti-pain effects were further strengthened by co-application of shTGFβ1. Together, these data suggest that M2 polarization of macrophages induced by both epigenetic modulation and suppressed production and release of TGFβ1 from polarized M2 macrophages, may have a demonstrable therapeutic effect on LDD.

• DNA methyltransferase 1 (DNMT1)
• aging
• lumbar disc degeneration (LDD)
• macrophage polarization
• transforming growth factor beta 1 (TGFβ1)

• Estrogen
• Intervertebral disc degeneration
• Low back pain
• Post menopause

• Estrogens/metabolism
• Humans
• Intervertebral Disc Degeneration/metabolism

• alginate
• biofunctionalization
• biomaterial characterization
• intervertebral disc
• platelet-rich plasma

The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD.

A study in rats highlights the role of mitochondria in intervertebral disc degeneration (IVDD), one of the most important and prevalent predisposing factors for lower back pain. Previous studies have shown that in IVDD, oxidative stress results in the gradual loss of cells in the inner part of vertebral discs which cushion the space between vertebrae. Sheng-Dan Jiang and Lei-Sheng Jiang at Shanghai Jiaotong University School of Medicine found that oxidative stress in these cells causes the selective degradation of mitochondria by preventing the expression of a protein that is essential for mitochondrial function. Overexpressing this protein in the intervertebral discs of rats with IVDD alleviated degeneration, suggesting that restoring mitochondrial function could be an effective therapeutic strategy for easing the pain associated with the condition.

• Anti-catabolic factors
• Cell supplementation
• Degenerative disc disease
• Drug delivery systems
• Endogenous repair
• Pro-anabolic factors

• Biomaterials, chemokines
• Disc degenerative disease
• Drug delivery systems
• Growth factors
• Low back pain
• Progenitor cells
• Regenerative medicine
• Stem cells
• miRNA

• Animals
• Cell- and Tissue-Based Therapy
• Humans
• Intervertebral Disc Degeneration/metabolism
• Intervertebral Disc Degeneration/therapy
• Mesenchymal Stem Cell Transplantation
• Regeneration

• Apoptosis
• Blood vessel
• Endplate
• Intervertebral disk degeneration
• TUNEL

• Aging
• cellular senescence
• intervertebral disc degeneration

• P01 AG043376 NIA NIH HHS
• P30 AG044271 NIA NIH HHS
• R01 AG044376 NIA NIH HHS
• U19 AG056278 NIA NIH HHS

• growth factor
• intervertebral disc
• intervertebral disc disease
• tissue engineering

• Adult
• Aged
• Aggrecans/metabolism
• Apoptosis
• Cartilage/metabolism
• Cell Cycle
• Collagen Type II/metabolism
• Cytokines/metabolism
• Estradiol/pharmacology
• Estrogen Receptor alpha/metabolism
• Female
• Flow Cytometry
• Humans
• Intervertebral Disc/metabolism
• Intervertebral Disc Degeneration/genetics
• Intervertebral Disc Degeneration/metabolism
• Luciferases/metabolism
• Male
• MicroRNAs/metabolism
• Middle Aged
• Polymerase Chain Reaction
• Young Adult

• Back pain
• fullerol
• inflammation
• intervertebral disc degeneration
• link N peptide

• Animals
• Annulus Fibrosus/metabolism
• Annulus Fibrosus/pathology
• Collagenases/biosynthesis
• Cyclooxygenase 2/biosynthesis
• Extracellular Matrix/metabolism
• Extracellular Matrix/pathology
• Extracellular Matrix Proteins/pharmacology
• Fullerenes/pharmacology
• Interleukin-1alpha/biosynthesis
• Interleukin-6/biosynthesis
• Intervertebral Disc Degeneration/drug therapy
• Intervertebral Disc Degeneration/metabolism
• Intervertebral Disc Degeneration/pathology
• Male
• Peptides/pharmacology
• Proteoglycans/pharmacology
• Rabbits

• R01 AR064792 NIAMS NIH HHS
• R03 AR053653 NIAMS NIH HHS
• R21 AR057512 NIAMS NIH HHS

• IVDJD
• PRGF
• PRP
• disc–bone crosstalk
• growth factors
• inflammation
• modic changes
• plasma rich in growth factors
• vertebral endplate

In vitro cell culture model.

To investigate the effect of small interfering RNA (siRNA) on Fas expression, apoptosis, and proliferation in serum-deprived rat disc cells.

Synthetic siRNA can trigger an RNA interference (RNAi) response in mammalian cells and precipitate the inhibition of specific gene expression. However, the potential utility of siRNA technology in downregulation of specific genes associated with disc cell apoptosis remains unclear.

Rat disc cells were isolated and cultured in the presence of either 10% fetal bovine serum (FBS) (normal control) or 0% FBS (serum deprivation to induce apoptosis) for 48 hours. Fas expression, apoptosis, and proliferation were determined. Additionally, siRNA oligonucleotides against Fas (Fas siRNA) were transfected into rat disc cells to suppress Fas expression. Changes in Fas expression were assessed by reverse transcription-polymerase chain reaction and semiquantitatively analyzed using densitometry. The effect of Fas siRNA on apoptosis and proliferation of rat disc cells were also determined. Negative siRNA and transfection agent alone (Mock) were used as controls.

Serum deprivation increased apoptosis by 40.3% (p<0.001), decreased proliferation by 45.3% (p<0.001), and upregulated Fas expression. Additionally, Fas siRNA suppressed Fas expression in serum-deprived cultures, with 68.5% reduction at the mRNA level compared to the control cultures (p<0.001). Finally, Fas siRNA–mediated suppression of Fas expression significantly inhibited apoptosis by 9.3% and increased proliferation by 21% in serum-deprived cultures (p<0.05 for both).

The observed dual positive effect of Fas siRNA might be a powerful therapeutic approach for disc degeneration by suppression of harmful gene expression.

• Apoptosis
• Cell proliferation
• Disc cells
• Fas
• Small interfering RNA

Several animal studies have demonstrated the positive effects of platelet-rich plasma (PRP) on disc degeneration retardation. The present meta-analysis was to verify the efficacy of PRP in retarding disc degeneration in animal.

Relevant studies were identified and evaluated according to our inclusion and exclusion criteria. The standardized mean difference (SMD) and related 95% confidence interval (95% CI) were estimated to assess PRP efficiency.

In total, eleven studies were included in this meta-analysis. Significant differences were found in the PRP treatment group, which showed increased disc height (SMD = 2.66, 95% CI: 1.86, 3.47, p = 0.000), increased MRI T2 signal intensity (SMD = −3.29, 95% CI: −4.44, −2.13, p = 0.000), and decreased histological degeneration grade (SMD = −4.28, 95% CI: −5.26, −3.30, p = 0.000). However, no significant increase in collagen II expression was found (SMD = 25389.74, 95% CI: −27585.72, 78365.21, p = 0.348). Apart from the subgroup analysis of the disc height based on animal species (pig) and disc degeneration model (chymopapain induction), other subgroup analysis based on animal species (rabbit and rat), study design, disc degeneration model, and follow-up period demonstrated that PRP treatment can significantly restore disc height and increase MRI T2 signal intensity.

PRP treatment is potentially effective in restoring disc height of rodent rabbit and rat, reducing histological degeneration grade, and increasing MRI T2 image signal. PRP injection may be promising therapy for retarding disc degeneration.

Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I–III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.

• PRP
• artemin
• chemonucleolysis
• chronic low back pain
• clinical trials
• new therapy
• stem cells
• tanezumab

• animal model
• apoptosis
• chondroptosis
• intervertebral disc degeneration

• Biología del disco intervertebral
• Disco intervertebral
• Intervertebral disc
• Intervertebral disc biology
• Intervertebral disc mechanobiology
• Mecanobiología del disco intervertebral
• Mecanoproteínas en el disco intervertebral
• Mechanoproteins in the intervertebral disc

In vitro cell culture model.

To investigate the effects of RNA interference (RNAi) on p75 expression and viability of rat notochordal cells treated with serum deprivation.

RNAi enables the inhibition of specific genes by sequence-specific gene silencing using a double-stranded RNA.

Notochordal cells were isolated, cultured, and placed in 10% (control) or 0% (apoptosis-promoting) fetal bovine serum (FBS) for 48 hours. The expression of p75, apoptosis, and cell proliferation were determined. To suppress p75 expression, a small interfering RNA (siRNA) was synthesized against p75 (p75 siRNA) and transfected into cells. The suppression of p75 mRNA expression was investigated using the reverse transcription-polymerase chain reaction. The degree of p75 suppression was semiquantitatively analyzed using densitometry. The effect of p75 siRNA on apoptosis and proliferation of cells was determined. Solutions of an unrelated siRNA and transfection agent alone served as controls.

Serum deprivation significantly increased apoptosis by 40.3%, decreased proliferation of notochordal cells by 45.3% (both, p<0.001), and upregulated p75 expression. The p75 siRNA suppressed p75 expression in cells cultured in 0% FBS. The rate of suppression by p75 siRNA of p75 mRNA was 72.9% (p<0.001). Suppression of p75 expression by p75 siRNA inhibited apoptosis by 7% and increased proliferation by 14% in cells cultured in 0% FBS (both, p<0.05).

siRNA-mediated suppression of p75 inhibited apoptosis and increased proliferation of notochordal cells under conditions of serum deprivation, suggesting that RNAi might serve as a novel therapeutic approach for disc degeneration caused by insufficient viability of disc cells through the suppression of the expression of harmful genes.

• Notochordal cells
• RNA interference
• Viability
• p75

Biologic-based treatment strategies for musculoskeletal diseases have gained traction over the past 20 years as alternatives to invasive, costly, and complicated surgical interventions. Spinal degenerative disc disease (DDD) is among the anatomic areas being investigated among this group, notably due to its high incidence and functional debilitation. In this review, we report the literature encompassing the use of biologic-based therapies for DDD. Articles published between January 1995 and November 2015 were reviewed, with a subset meeting the primary and secondary inclusion criteria of clinical trial results that could be sub-classified into bimolecular, cell-based, or gene therapies, as well as studies investigating the utility of allogeneic and tissue-engineered intervertebral discs. Ongoing clinical trials that have not yet published results are also mentioned to present the current state of the field. This exciting area has demonstrated positive and encouraging results across multiple strategies; thus, future bimolecular and regenerative techniques and understanding will likely lead to an increase in the number of human clinical trials assessing these therapies.

• biomolecular therapy
• degenerative disc disease
• degenerative spine
• gene therapy
• spine
• spine surgery
• tissue engineering

• 3D culture system
• intervertebral disc
• molecular phenotype
• notochordal cells
• nucleus pulposus

• Annulus fibrosus
• Disc degeneration
• FGF-2
• Mitogen
• Morphogen
• TGF-β1
• Tissue engineering

Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

• Stem cells
• Intervertebral disc degeneration
• Spine
• Tissue engineering
• Cell therapy

The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD.

• Intervertebral disc degeneration
• anti-senescence therapy
• cause-dependent molecular pathways
• disc cell senescence
• senescence-associated secreted phenotype

• Chronic pain
• Future therapy
• Pain management
• Platelet-rich plasma

• Chronic Pain/therapy
• Evidence-Based Medicine/trends
• Humans
• Pain Management/trends
• Pain Measurement/trends
• Platelet-Rich Plasma
• Treatment Outcome

Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge.

The aim of our study was to assess the clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations (one intradiscal, one intra-articular facet, and one transforaminal epidural injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF-Endoret which has been shown to be an efficient treatment to reduce joint pain.

The study was designed as an observational retrospective pilot study. Eighty-six patients with a history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited between December 2010 and January 2012.

One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86 patients with chronic LBP in the operating theater setting.

Descriptive statistics were performed using absolute and relative frequency distributions for qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman statistical test was used to determine the possible differences between baseline and different follow-up time points on pain reduction after treatment.

Pain assessment was determined using a visual analog scale (VAS) at the first visit before (baseline) and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF-Endoret injections showed a statistically significant drop from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively, with respect to all the time evaluations (P < 0.0001) except for the pain reduction between the 3^rd and 6^th month whose signification was lower (P < 0.05). The analysis of the VAS over time showed that at the end point of the study (6 months), 91% of patients showed an excellent score, 8.1% showed a moderate improvement, and 1.2% were in the inefficient score.

Fluoroscopy-guided infiltrations of intervertebral discs and facet joints with PRGF in patients with chronic LBP resulted in significant pain reduction assessed by VAS.

• Chronic low back pain
• fibrin matrix
• plasma rich in growth factors
• platelet-rich plasma
• visual analog scale

Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells.

Thirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting.

Cells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II.

SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease.