Effects of ultrasound therapy on the synovial fluid proteome in a rabbit surgery-induced model of knee osteoarthritis

Abstract

Background Ultrasound (US) therapy may improve osteoarthritis symptoms. We investigated the effects of US on the synovial fluid (SF) proteome in a rabbit knee osteoarthritis (KOA) model to explore its therapeutic mechanisms. Methods Sixteen healthy 6-month-old New Zealand white rabbits (eight male, eight female), weighing 2.5–3.0 kg, were randomly divided into groups A and B with eight rabbits per group. Both groups were subjected to right anterior cruciate ligament transaction. Six weeks after surgery, we treated the operated knee joint of group A rabbits with US and of group B rabbits with sham US for 2 weeks. The proteomes of knee joint SF from groups A and B rabbits were then analyzed using a label-free mass spectrometry (MS) quantification method. Results We identified 19 protein sequences annotated by 361 Gene Ontology (GO) items. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database of rabbit protein sequences, we then annotated the KO numbers of homologous/similar proteins to 32 relevant KEGG pathways. We extracted 10 significantly differentially expressed proteins among the 32 relevant KEGG messages/metabolism pathways. The proteins whose levels were decreased were apolipoprotein A-I (AopA-1), transferrin (TF), carboxypeptidase B2 (CBP2), arylesterase/paraoxonase (PON), fibrinogen alpha chain, and alpha-2-macroglobulin (A2M). The proteins whose levels were increased were molecular chaperone HtpG/heat shock proteins (htpG, HSP90A), decorin (DCN), pyruvate kinase (PK, pyk), and fatty acid-binding protein 4/adipocyte (FABP4, aP2). Conclusions US therapy can alter protein levels in SF, which can decrease AopA-1, TF, CBP2, PON, fibrinogen alpha chain and A2M protein levels, and increase HtpG/HSP90A, DCN, PK/PKY, and FABP4/aP2 protein levels in SF of KOA, suggesting that the therapeutic mechanisms of US therapy on KOA may occur through changes in the SF proteome.

Identification of Candidate Synovial Fluid Biomarkers for the Prediction of Patient Outcome After Microfracture or Osteotomy

“…However, it has been identified in several other relevant proteomic studies that assessed (1) the membrane proteins of equine articular chondrocytes 23 ; (2) the secretome of cultured chondrocytes 29 ; (3) the SF of patients with either rheumatoid arthritis or OA 2 ; and (4) the SF of rabbits subjected to ACL transection compared with sham injury. 21 Together, these data suggest that this protein may be secreted from chondrocytes into the SF, but how changes in the abundance of this protein within the SF relate to OA disease severity or progression requires further investigation.…”

Correlation of Synovial Tissues Protein Abundance With Age and Menopause in Osteoarthritis and Knee Joint Injury of Female Patients

“…Therefore, more and more investigators focus on proteomics studies investigating the componence and potential roles of synovial uid [14,15,16,17,18]. Animal models of osteoarthritis are also used in recent studies to understand the pathophysiology of OA and develop successful treatment of OA [19,20]. However, the role of ST of the knee joint in the onset and development of OA remains largely unknown.…”

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

“…However, abundances of these uncharacterised proteins could not be validated using antibody methodologies. Recently, a study investigating the SF proteome of a surgeryinduced OA model in rabbits identified reduced levels of immunoglobulin heavy chain protein compared to sham controls (69). Immunoglobulins have previously been identified within superficial articular cartilage layers of a proportion of OA patients as well as elevated levels found within the synovial membrane of dogs diagnosed with cranial cruciate ligament rupture (70,71).…”