Table 1.
Final studies with authors, year of publication, design and key findings.
| Authors | Year | Study Design | Key Findings | Species | Sample |
|---|---|---|---|---|---|
| Ding et al. [28] | 2013 | MAPK pathway analyzed using PCR, Western blot and IHC. | p38 and ERK1/2 signalling plays a distinct role in leptin-induced AF cells terminal differentiation. | Rat | AF |
| Gruber et al. [29] | 2007 | Disc tissue from n = 7 young (normal); n = 29 adults (degenerative) examined. | Leptin and its receptor are present in human annulus cells. | Human | AF |
| Khabour et al. [30] | 2014 | n = 168 LDD patients and n = 122 healthy controls were genotyped for rs266729 and rs2241766 SNPs and measured for plasma levels of adiponectin. | Adiponectin was elevated in patients with LDD. However, SNPs in the ADIPOQ gene were not associated with LDD. | Human | Plasma |
| Koerner et al. [31] | 2014 | Degenerative (n = 7) and normal disc tissue (n = 2) was separated into anterior and posterior AF. Expression levels of 42 cytokines were determined and compared between anterior vs. posterior AF. | The posterior AF expressed increased levels of IL-4, IL-5, IL-6, M-CSF, TNF-β, EGF, IGF 1, angiogenin and leptin compared with the anterior AF in patients with degenerative discs. | Human | AF |
| Li et al. [32] | 2014 | NP cells isolated from n = 7 patients, treated with leptin. RhoA signalling in NP cells was determined. Protein expression of LIMK1 and cofilin-2 was analyzed. F-actin cytoskeletal reorganization was assessed. | Leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in NP cells. | Human | NP |
| Li et al. [33] | 2012 | Effects of leptin on the proliferation of primary cultured human NP cells (n = 8) and the underlying mechanism. | Leptin induced human NP cell proliferation and cyclin D1 expression via activation of JAK/STAT3, PI3K/Akt or MEK/ERK signaling. | Human | NP |
| Li et al. [34] | 2013 | Do NP tissues and cells express leptin receptors (OBRa and OBRb) and whether leptin affects the organization and expression of major cytoskeletal elements in NP cells (n = 45). | mRNA and proteins of OBRa and OBRb were expressed in all NP tissues and cells, and OBRb expression was correlated with body weight. Increased expression of beta-actin, vimentin and reorganization of F-actin were evident in leptin-stimulated NP cells. | Human | NP |
| Li et al. [35] | 2014 | Effects of leptin on the expression of aggrecan and ADAMTSs in primary human NP cells (n = 4). | Leptin induced p38 to upregulate ADAMTSs and thereby promoting aggrecan degradation in human NP cells. | Human | NP |
| Li et al. [42] | 2017 | Resistin and CCL4 expression measured in degenerated human NP tissue. TLR-4, p38-MAPK, and NF-kappaβ signaling pathways studied. | Expression of resistin and CCL4 was elevated in degenerated NP tissue. Resistin via TLR4 receptor increased the expression of CCL4 through p38-MAPK and NF-kappaβ signaling pathways. | Human | NP |
| Liu et al. [41] | 2016 | Transcriptional activity, gene expression, and protein levels of ADAMTS-5 were measured in resistin-exposed NP cells along with detection of activation of p38 MAPK. | p38-MAPK signaling pathway was activated after exposure to resistin. p38 inhibitor decreased the upregulation of ADAMTS-5 by resistin. | Rat | NP |
| Miao et al. [36] | 2015 | Effects of leptin on the expression of degeneration-associated genes in n = 30 rat NP cells, and its possible mechanism. | Leptin promoted catabolic metabolism in the rat NP cells via the MAPK and JAK2/STAT3 pathways. | Rat | NP |
| Terashima et al. [40] | 2016 | Adiponectin and adiponectin receptors AdipoR1 and AdipoR2 were detected in disc tissue (n = 4, Humans) and (n = 21, Rats). IL-1beta and/or adiponectin-treated rat NP and AF tissues were evaluated for mRNA expression of TNF-alpha and IL-6. | AdipoR1 and AdipoR2 were widely expressed in both human and rat IVD tissues, were inversely related to disease severity. TNF-alpha expression in the IL-1beta + Ad group was significantly lower than that in the IL-1beta group in both NP and AF cells. | Human, Rat | NP, AF |
| Yuan et al. [39] | 2018 | Examined the expression levels of and effect of adiponectin on TNF-alpha in IVD tissues and isolated NP cells. | Adiponectin levels were downregulated, while AdipoR1 and AdipoR2 expression was upregulated in degenerated IVD tissues and NP cells compared to healthy controls. TNF-alpha production by degenerated NP cells was downregulated by adiponectin administration. | Human | NP |
| Zhang et al. [38] | 2018 | Human degenerative NP cells were extracted and cultured, then treated with leptin, leptin inhibitor and leptin neutralizing antibody and expressions of LC3 II/I, Beclin-1 were studied and change of apoptosis rate was detected. Leptin/bafilomycin A and (PI3K)/(MEK) inhibitor-treated cells were used to detect the expressions of LC3II/I, cleaved caspase 3, apoptosis rate, Akt and Erk1/2 signal pathway. | Leptin-treated cells showed increased expressions of LC3II/I and Beclin-1 and decreased apoptosis rate. Leptin inhibitor or neutralizing antibody showed the opposite results. Bafilomycin A increased the expression of LC3II/I and apoptosis rate. Inhibition of Akt phosphorylation was partially offset by leptin while inhibition of Erk1/2 phosphorylation was not. | Human | NP |
| Zhao et al. [37] | 2008 | Determined the expression of leptin and its functional receptor in human herniated disc tissues (n = 45), and to elucidate whether leptin can stimulate rat NP cells to proliferate in vitro. | Disc cells express leptin and its functional receptor. Leptin stimulated proliferation of disc cells in vitro. | Human, Rat | NP |
Janus Kinase 2 (JAK2), Signal transducer and activator of transcription (STAT), Mitogen activating protein kinase (MAPK), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), proliferation cell nuclear antigen (PCNA), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), Leptin Receptor Long Form (OBRb), Ras homolog gene family member A (RhoA), matrix metalloproteinase (MMP), nucleus pulposus (NP), annulus fibrosus (AF), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-β), interleukin (IL), adiponectin receptor 1 (adipoR1), adiponectin receptor 2 (adipoR2), extracellular regulated protein kinases 1/2 (Erk1/2), phosphatidylinositol 3-kinase (PI3K), extracellular regulated protein kinases (MEK), light chain 3 (LC3), chemokine ligand 4 (CCL4), Toll-like receptor 4 (TLR-4), nuclear factor-kappa beta (NF-κβ), Intervertebral disc (IVD), Lumbar disc degeneration (LDD), Macrophage colony-stimulating factor (M-CSF), epidermal growth factor (EGF), Insulin-like growth factor 1 (IGF 1), Single nucleotide polymorphisms (SNPs), LIM domain kinase 1 (LIMK1), Rho-associated protein kinase (ROCK), Enzyme-linked immunosorbent assay (ELISA), Immunohistochemistry (IHC), Polymerase chain reaction (PCR).