Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

Wu, Xiexing; Liu, Yu; Guo, Xiaobin; Zhou, Wei; Wang, Liangliang; Shi, Jiawei; Tao, Yunxia; Zhu, Mo; Yang, Huilin; Mao, Haiqing

doi:10.1038/s41419-017-0151-z

Cited by 66 publications

(62 citation statements)

References 42 publications

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“…AF cells help to maintain the structural integrity through synthesizing and secreting normal and adequate extracellular matrix, whereas some intrinsic and extrinsic pathways activated by the detrimental pathological factors often induce AF cell apoptosis [12,13]. In the previous animal disc degeneration models [12,14], the number of apoptotic AF cells is significantly increased, indicating that AF cell apoptosis is promoted and involved in the progression of disc degeneration.…”

Section: Introductionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.

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Section: Introductionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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“…NF‐κB pathway has an essential role in IVDD pathogenesis . In the context inflammation caused by LPS, IκBα becomes phosphorylated, which triggers the translocation of p65.…”

Section: Discussionmentioning

confidence: 99%

“…NF-κB pathway has an essential role in IVDD pathogenesis. 37,38 In the context inflammation caused by LPS, IκBα becomes phosphorylated, which triggers the translocation of p65. Several researches have shown that p65 promotes transcription of inflammatory genes, for example PGE2, IL-6, COX-2, iNOS, and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD‐2 complex

Shang

Tang

et al. 2020

J Cellular Molecular Medi

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As a chronic musculoskeletal degeneration disease, intervertebral disc degeneration (IVDD) has been identified as a crucial cause for low back pain. This condition has a prevalence of 80% among adults without effective preventative therapy. Procyanidin B3 (Pro‐B3) is a procyanidin dimer, which is widely present in the human diet and has multiple functions, such as preventing inflammation. But the inhibiting effect of Pro‐B3 in IVDD development is still no known. Thus, our study aimed to demonstrate the therapeutical effect of Pro‐B3 in IVDD and explain the underlying mechanism. In vitro studies, human nucleus pulposus (NP) cells were isolated and exposed in lipopolysaccharide (LPS) to simulate IVDD development. Pro‐B3 pre‐treatment inhibited LPS‐induced production of inflammation correlated factors such as tumour necrosis factor α (TNF‐α), interleukin‐6 (IL‐6), prostaglandin E2 (PGE2) and Nitric oxide (NO). On the other hand, LPS‐medicated extracellular matrix (ECM) breakdown was blocked in Pro‐B3 treated NP cells. Additionally, Pro‐B3 treatment blocked the activation of NF‐κB/toll‐like receptor 4 pathway in LPS‐exposed NP cells. Mechanistically, Pro‐B3 could occupy MD‐2's hydrophobic pocket exhibiting high affinity for LPS to intervene LPS/TLR4/MD‐2 complex formation. In vivo, Pro‐B3 treatment prevented the loss of gelatin NP cells and structural damage of annulus fibrosus in rat IVDD model. In brief, Pro‐B3 is considered to be a treatment agent for IVDD.

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“…In general, NP cells produce extracellular matrix (ECM) including collagen II and proteoglycans, the main components of the gelatinous tissues of NP [20]. The gelatinous NP is essential for a functional disc, and degeneration of the NP is regarded as a crucial part of IVDD [40].…”

Section: Discussionmentioning

confidence: 99%

“…9A-C). In general, gelatinous NP is the main functional composition of IVD, and degeneration of the NP is regarded as a crucial part of intervertebral disc degeneration [20]. Sham group showed the structures of NP with strong immunoreactivity for aggrecan and weak immunoreactivity for MMP-13 and ADAMTS-4.…”

Section: Composition Changes Of Np At Protein Levelmentioning

confidence: 97%

Denosumab Alleviates Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion by Inhibiting Endplate Osteochondral Remodeling and Vertebral Osteoporosis in Ovariectomized Rats

Sun

Tian

Liu

et al. 2020

Preprint

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Background: Although adjacent segmental intervertebral disc degeneration (ASDD) is one of the most common complications after lumbar fusion, its exact mechanism remains unclear. As an antibody to RANKL, denosumab (Dmab) effectively reduces bone resorption and stimulates bone formation, which can increase bone mineral density (BMD) and improve osteoporosis. However, it has not been confirmed whether Dmab has a reversing or retarding effect on ASDD. Methods: Three-month-old female Sprague-Dawley rats that underwent L4–L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation four weeks after OVX surgery were given Dmab four weeks after PLF surgery (OVX+PLF+Dmab group). In addition, the following control groups were defined: Sham, OVX, PLF, and OVX+PLF (n=12 each).Then, manual palpation and X-ray were used to evaluate the state of lumbar fusion. The bone microstructure in the lumbar vertebra and endplate as well as the disc height index (DHI) of the L5/6 were evaluated by microcomputed tomography (μCT). The characteristic alterations of ASDD were identified via Safranin-O green staining staining. Osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining and the biomechanical properties of vertebra were evaluated. Aggrecan (Agg), metalloproteinase-13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) expression in the intervertebral disc were detected by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) analysis.Results: Manual palpation showed clear evidence of the fused segment’s immobility. Compared to the OVX+PLF group, more new bone formation was observed by X-ray examination in the OVX+PLF+Dmab group. Dmab significantly alleviated ASDD by retaining disc height index (DHI), decreasing porosity of endplate, and increasing the biomechanical properties and BMD of vertebra. TRAP staining results showed a significantly decreased number after Dmab treatment, especially in subchondral bone and cartilaginous endplate. Moreover, the results of protein and mRNA expression in intervertebral disc (IVD) showed that Dmab not only inhibited matrix degradation by decreasing MMP-13 and ADAMTS-4 but also promoted matrix synthesis by increasing Agg. Conclusions: These results suggest that Dmab may be a novel therapeutic target for the treatment of ASDD.

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Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-κB pathway in rats

Cited by 66 publications

References 42 publications

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD‐2 complex

Denosumab Alleviates Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion by Inhibiting Endplate Osteochondral Remodeling and Vertebral Osteoporosis in Ovariectomized Rats

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