Reduced Expression of Insulin-like Growth Factor 1 Receptor Leads to Accelerated Intervertebral Disc Degeneration in Mice

Objectives. Aberrant transforming growth factor β (TGFβ) activation is detrimental to both nucleus pulposus (NP) cells and cartilage endplates (CEPs), which can lead to intervertebral disc degeneration (IDD). Ligustrazine (LIG) reduces the expression of inflammatory factors and TGFβ1 in hypertrophic CEP to prevent IDD. In this study, we investigate the effects of LIG on NP cells and the TGFβ signaling. Design. LIG was injected to the lumbar spinal instability (LSI) mouse model. The effect of LIG was evaluated by intervertebral disc (IVD) score in the LSI mouse model. The expression of activated TGFβ was examined using immunostaining with pSmad2/3 antibody. The upright posture (UP) rat model was also treated and evaluated in the same manner to assess the effect of LIG. In ex vivo study, IVDs from four-week old mice were isolated and treated with 10−5, 10−6, and 10−7 M of LIG. We used western blot to detect activated TGFβ expression. TGFβ-treated human nucleus pulposus cells (HNPCs) were cotreated with optimized dose of LIG in vitro. Immunofluorescence staining was performed to determine pSmad2/3, connective tissue growth factor (CCN2), and aggrecan (ACAN) expression levels. Results. IVD score and the percentage of pSmad2/3+ NP cells were low in LIG-treated LSI mice in comparison with LSI mice, but close to the levels in the Sham group. Similarly, LIG reduced the overexpression of TGFβ1 in NP cells. The inhibitory effect of LIG was dose dependent. A dose of 10−5 M LIG not only strongly attenuated Smad2/3 phosphorylation in TGFβ-treated IVD ex vivo but also suppressed pSmad2/3, CCN2, and ACAN expression in TGFβ-treated NP cells in vitro. Conclusions. LIG prevents IDD via suppression of TGFβ overactivation in NP cells.

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Transport of Insulin-Like Growth Factor 1 in Intervertebral Disc: Effect of Binding Interactions and Inhomogeneous Distribution of Binding Proteins in Annulus Fibrosus and Nucleus Pulposus

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19469 ◽

2010 ◽

Author(s):

Francesco Travascio ◽

Chun Yuh Huang ◽

Wei Yong Gu

Keyword(s):

Growth Factor ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Reactive Transport ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Igf Binding Proteins ◽

Binding Interactions

The intervertebral disc (IVD), being the largest avascular structure in human body, receives nourishment from the vascular network present near its periannular surface and at cartilage endplates (CEPs). It is believed that insufficient nutritional supply is a major cause for disc degeneration [1]. Understanding the mechanisms of solute transport in IVD is crucial for elucidating the etiology of disc degeneration, and to develop strategies for tissue repair (in vivo), and tissue engineering (in vitro). Transport in IVD is complex and involves a series of electromechanical, chemical, and biological coupled events. This study focused on the implications of solute-tissue reversible binding reactions on transport phenomena in the disc. A two dimensional (2D) finite element model was developed to predict diffusive-reactive transport in IVD. The numerical model was used to simulate transport of insulin-like growth factor 1 (IGF-1) in IVD, in the presence of binding interactions between IGF-1 and IGF-binding proteins (IGFBP-3) located on the extracellular matrix (ECM) of the disc.

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Lentivirus‑mediated transfer of gene encoding fibroblast growth factor‑18 inhibits intervertebral disc degeneration

Experimental and Therapeutic Medicine ◽

10.3892/etm.2021.10288 ◽

2021 ◽

Vol 22 (2) ◽

Author(s):

Sheng Lu ◽

Chao-Wei Lin

Keyword(s):

Growth Factor ◽

Intervertebral Disc ◽

Fibroblast Growth Factor ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Fibroblast Growth ◽

Gene Encoding

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Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

Life ◽

10.3390/life11101054 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1054

Author(s):

Wen-Cheng Lo ◽

Chun-Chao Chang ◽

Chun-Hao Chan ◽

Abhinay Kumar Singh ◽

Yue-Hua Deng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Growth Factor ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Transforming Growth Factor ◽

Disc Height ◽

Therapeutic Effects

Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.

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