Comparative analysis of serum proteomes of degenerative scoliosis

Abstract

Degenerative scoliosis (DS) is an important degenerative lumbar disease causing spinal dysfunction and affecting the quality of life of the elderly, and is associated not only with severe back or leg pain but also with complicated surgical outcomes. The pathogenesis of DS is still unknown. Therefore, it is very important to ascertain the etiology of degenerative scoliosis and establish related molecular markers predicting and controlling the scoliosis. For the first time, we used two-dimensional fluorescence DIGE to compare the serum proteome profiles of 12 DS patients and controls. Proteins found to be differentially expressed were identified by MALDI-TOF mass spectrometric analysis, coupled with database interrogation. Eleven spots that were differentially expressed in the sera of DS patients were found, and eight gene products were identified among these spots. Clusterin, CLU cDNA FLJ57622, ALB cDNA FLJ50830, Hypothetical short protein, HLA-A MHC class 1 antigen. (Fragment), ALB 23 kDa protein, Isoform 1 of G proteinregulated inducer of neurite outgrowth 1 (GPRIN I)and Ficolin-3 were down-regulated in the sera of DS patients. The decreased levels of Clusterin and Ficolin-3 were confirmed by Western blot. The information obtained with this proteomic analysis will be very useful in understanding the pathophysiology of DS as well as in finding candidates as drug targets of DS. These results may provide a novel approach for the pathogenesis study of DS. Keywords: degenerative; scoliosis; serum; DIGE; proteomics Degenerative scoliosis (DS) refers to scoliotic curves developing after skeletal maturity without previous history of scoliosis. Scoliosis occurs de novo in later life and is associated not only with deformity but also with severe back or leg pain.1 With the lifestyle changes of the elderly, DS has become an important degenerative lumbar disease causing spinal dysfunction and affecting quality of life of the elderly.The pathogenesis of DS is still unknown. Osteoporosis has long been implicated in the pathogenesis of elderly patients with DS. Vanderpool et al.2 found scoliosis in 36% of osteoporotics compared to 6% in age-matched normals. However, Robin et al.3 were unable to find a significant correlation between scoliosis and osteoporosis.Although osteoporosis, asymmetric degenerative disc disease, facet tropism and inheritance have been implicated as factors in the development of DS, none has been shown to be directly related. Most of the current research on the DS is about the treatment of this disease, and the basic research on the etiology is few. Furthermore, there was no molecular biology study reported. Therefore, It is very important to ascertain the etiology of DS and establish related molecular markers predicting and controlling the scoliosis. Proteomics analysis is currently considered to be a powerful tool for global evaluation of protein expression, and proteomics has been widely applied in analysis of diseases, especially in fields of cancer research. Two-dimensional (2D) gel elect...

Identification of Proteins from Interstitium of Trapezius Muscle in Women with Chronic Myalgia Using Microdialysis in Combination with Proteomics

“…Proteins that are involved in pain are important to investigate due to the fact that they can act as signal substances, activate the formation of algesics and control nociceptive processes. The number of studies investigating the human proteome in body fluids and tissues in human chronic pain conditions are limited e.g., [17]–[22], [35]–[37]. There are also a few examples of proteomic studies in acute pain e.g., acute coronary syndrome [38], after eccentric exercises [39] and experimental cutaneous injury [40].…”

Radiographic Parameters in Adult Degenerative Scoliosis and Different Parameters Between Sagittal Balanced and Imbalanced ADS Patients

“…Due to the rapid increase of prevalence of ADS, more and more attention have been paid to this disease, including the researches of etiology, 4 , 5 patients’ demographics, 6 clinical and radiological evaluation, 7 conservation treatment and surgery. 8 – 10 Only a few studies 3 , 6 , 11 have been performed to make a description of some patients’ demographics and radiographic parameters.…”

Genetics Underlying an Individualized Approach to Adult Spinal Disorders

“…Proteomic analyses of the sera of patients with DS have identified 11 proteins that are differentially expressed in such patients, 2 of which were secondarily confirmed with Western blot analyses, CLU (also known as apolipoprotein J, testosterone-repressed prostate message-2, SP 40-40, complement lysis inhibitor, gp80, glycoprotein III, and sulfate glycoprotein-2) and Ficolin-3 (also named Hakata antigen, thermolabile β-2 macroglycoprotein, thermolabile substance, and H-ficolin) (83). Both of these proteins have been suggested to have roles in autoimmunity, although they both likely have multiple roles in the human body and their association is non-specific.…”

“…It is thought that distinct genetic characteristics define these seemingly similar, but quite clinically different syndromes. Our systematic review identified six works in the literature (Table 2) (52, 83–87) that identified genetic contributions for DS. The quality of the data is relatively limited (Level III studies) but provides some insight into potential genetic mechanisms for disease pathogenesis that could potentially be used in future studies.…”