Adrenoceptor Expression during Intervertebral Disc Degeneration

Abstract

Healthy and degenerating intervertebral discs (IVDs) are innervated by sympathetic nerves, however, adrenoceptor (AR) expression and functionality have never been investigated systematically. Therefore, AR gene expression was analyzed in both tissue and isolated cells from degenerated human IVDs. Furthermore, human IVD samples and spine sections of wildtype mice (WT) and of a mouse line that develops spontaneous IVD degeneration (IVDD, in SM/J mice) were stained for ARs and extracellular matrix (ECM) components. In IVD homogenates and cells α1a-, α1b-, α2a-, α2b-, α2c-, β1-, and β2-AR genes were expressed. In human sections, β2-AR was detectable, and its localization parallels with ECM alterations. Similarly, in IVDs of WT mice, only β2-AR was expressed, and in IVDs of SM/J mice, β2AR expression was stronger accompanied by increased collagen II, collagen XII, decorin as well as decreased cartilage oligomeric matrix protein expression. In addition, norepinephrine stimulation of isolated human IVD cells induced intracellular signaling via ERK1/2 and PKA. For the first time, the existence and functionality of ARs were demonstrated in IVD tissue samples, suggesting that the sympathicus might play a role in IVDD. Further studies will address relevant cellular mechanisms and thereby help to develop novel therapeutic options for IVDD.

Engineered Peptide-Functionalized Hydrogels Modulate the RNA Transcriptome of Human Nucleus Pulposus Cells In Vitro

“…Similarly, ADRA2C and SST have been found to be biomarkers in chronic pain for temporomandibular disorder and low back pain [87][88][89] . Although a study found low ADRA2C expression in cartilage, a recent report found a decrease in expression of this protein was associated with IVD degeneration 51,90 . GPR162 (also known as GRCA) has been found in neurons, cartilage, and NP cells 83,86,91,92 .…”

“…3d). These two markers were chosen for validation as ADRA2C has been observed to be downregulated in degenerative discs 51 and OXTR has been studied in the context of musculoskeletal development, neurogenic pain and inflammation [52][53][54] and have known agonists and antagonists [55][56][57] . The protein expression data replicated the results observed through RNA sequencing and confirmed that the differential expression of these two markers was observed at the transcriptomic and proteomic levels.…”

Correlation between Adrenoceptor Expression and Clinical Parameters in Degenerated Lumbar Intervertebral Discs

“…Following the results of Lorenz et al, the presence of sympathetic nerve fibers and the expression of ARs was detected in healthy and degenerated IVDs [ 28 , 29 , 30 ]. In addition, an enhanced and expanded expression of β2-AR in highly degenerated IVDs of mice was found [ 22 ]. To obtain more detailed information about the AR expression in IVDD, clinical and radiological parameters of the patients were collected and investigated to determine whether there is a correlation with AR expression.…”

“…With regard to the fact that physiology and extracellular matrix in degenerated articular cartilage and IVD tissue share several similarities [ 20 ], Barczewska et al proved the presence of sympathetic nerve fibers in degenerated bovine IVD-tissue [ 21 ]. On the basis of these results, Kupka et al were able to detect AR gene expression in tissue of degenerated human IVDs and an induction of intracellular signaling pathways through the sympathetic neurotransmitter NE that activates ARs [ 22 ].…”

Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus

“…Degeneration of IVD is a complex process and its association with low back pain (LBP) is not very well known; however, studies have shown aging, genetic, occupation, and IVD disruption may lead to IVD degeneration causing LBP [ 2 , 3 , 4 , 5 ]. LBP is a prevalent and debilitating condition with extensive socio-economic impacts affecting the quality of life, reflected by the years lived with disability (YLD).…”