Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model

Abstract

BackgroundAdipose tissue is a large endocrine organ known to secret adiponectin, which has anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Adiponectin is widely involved in systemic disease, diabetes mellitus, and cardiac infraction. This study aimed to investigate the involvement of adiponectin in intervertebral disc (IVD) degeneration.MethodsAdipose and IVD tissues were obtained from human patients undergoing surgery (n = 4) and from skeletally mature Sprague–Dawley rats (n = 21). Tissues were stained immunohistochemically for adiponectin and adiponectin receptors AdipoR1 and AdipoR2. Changes in adiponectin receptor expression with IVD degeneration severity were then investigated using a rat tail temporary compression model. Rat IVD tissues were stained immunohistochemically with AdipoR1 or AdipoR2, and immunopositive cell percentages were calculated. Rat nucleus pulposus (NP) and annulus fibrosus (AF) tissues were isolated separately and treated with recombinant adiponectin (Ad 0.1 or 1.0 μg/ml) and/or interleukin-1 beta (IL-1β) (0.2 μg/ml) for 24 h. The four groups were as follows: control group (no treatment), IL-1β group (IL-1β-only treatment), IL-1β+Ad (0.1) group (IL-1β and adiponectin [0.1 μg/ml] treatment), and IL-1β+Ad (1.0) group (IL-1β and adiponectin [1.0 μg/ml]). Real-time reverse transcription-polymerase chain reaction was performed to evaluate messenger-RNA (mRNA) expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).ResultsAdiponectin was widely expressed in human subcutaneous and epidural adipose tissue. In rat IVD tissue, adiponectin was not observed in NP and AF. However, both AdipoR1 and AdipoR2 were widely expressed in both human and rat IVD tissues, with no significant differences in expression levels between receptors. Furthermore, expression levels of AdipoR1 and AdipoR2 were gradually decreased with increased IVD degeneration severity. Interestingly, mRNA expression levels of TNF-α and IL-6 were significantly upregulated by IL-1β stimulation. TNF-α expression in the IL-1β+Ad 1.0 group was significantly lower than that in the IL-1β group in both NP and AF cells (P < 0.05). Finally, IL-6 expression was not affected by adiponectin treatment in IVD cells.ConclusionsThis study investigated for the first time the expression of adiponectin receptors in human and rat IVD cells. The findings indicate that adiponectin produced by the systemic or epidural adipose tissue may be involved in the pathomechanism of IVD degeneration.

The Role of Adipokines in Intervertebral Disc Degeneration

“…All studies were published from 2007 onwards and included age groups ranging from young [ 29 , 35 ], adult [ 28 , 30 , 32 , 33 , 34 , 35 , 37 ] to elderly [ 31 ] cohorts. All were in vitro studies focusing on a range of topics from receptor identification [ 29 , 37 ], pathway analysis [ 28 , 32 , 34 , 36 , 38 , 40 , 41 , 42 ], genetic associations [ 30 ] and proteonomics [ 31 , 33 , 37 ]. Four human studies compared results between cases and controls [ 29 , 30 , 31 , 39 ].…”

“…Ten of 15 studies evaluated leptin and/or their receptors via utilizing different methodologies ranging from but not limited to Western blot (WB), immunohistochemistry (IHC), polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) [ 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Additionally, three studies assessed adiponectin [ 30 , 39 , 40 ], while two studies assessed resistin [ 41 , 42 ].…”

“…Eleven of 15 studies (seven human [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]; two animal [ 28 , 36 ] and two both [ 37 , 40 ]) studied nucleus of the intervertebral disc tissue [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], whereas three (one animal [ 28 ] and two human [ 29 , 31 ]) studies evaluated annulus of the intervertebral disc tissue [ 28 , 29 , 31 ]. The remaining one study only tested plasma samples [ 30 ].…”

“…Publication types not meeting the inclusion criteria were discarded. After excluding 11 abstracts, one editorial, one review and seven records based on title, abstract and publication information; 15 records were included in the final review ( Figure 2 , Table 1 ) [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Full-length articles of the remaining 15 records were obtained and screened.…”

The Establishment of Intervertebral Endplate Degeneration: A Novel in-vivo Diurnal-Axial Controllable Loading Model in Rat Tail

“…Further, the degree of degeneration heavily depends on time and the extent of bending force applied to the rat tail. Another classic model, Ilizarov-type compressive model, was widely used by many researchers due to its reliable installation and satisfactory modeling results [11,[22][23][24]. However, a set of springs were mainly used in these studies as the provider of compression loads.…”