COL2A1 and Caspase-3 as Promising Biomarkers for Osteoarthritis Prognosis in an Equus asinus Model

Abstract

Osteoarthritis (OA) is one of the most degenerative joint diseases in both human and veterinary medicine. The objective of the present study was the early diagnosis of OA in donkeys using a reliable grading of the disease based on clinical, chemical, and molecular alterations. OA was induced by intra-articular injection of 25 mg monoiodoacetate (MIA) as a single dose into the left radiocarpal joint of nine donkeys. Animals were clinically evaluated through the assessment of lameness score, radiographic, and ultrasonographic findings for seven months. Synovial fluid and cartilage samples were collected from both normal and diseased joints for the assessment of matrix metalloproteinases (MMPs) activity, COL2A1 protein expression level, and histopathological and immunohistochemical analysis of Caspase-3. Animals showed the highest lameness score post-induction after one week then decreased gradually with the progression of radiographical and ultrasonographic changes. MMP activity and COL2A1 and Caspase-3 expression increased, accompanied by articular cartilage degeneration and loss of proteoglycan. OA was successfully graded in Egyptian donkeys, with the promising use of COL2A1and Caspase-3 for prognosis. However, MMPs failed to discriminate between early and late grades of OA.

CGRP Regulates Nucleus Pulposus Cell Apoptosis and Inflammation via the MAPK/NF‐κB Signaling Pathways during Intervertebral Disc Degeneration

“…As shown in our results, the gene transcription of PCNA was dose-dependently decreased by CGRP in human NP cells. Cleaved-caspase 3, Bax, and Bcl-2 are critical markers to reflect cell apoptosis [ 43 , 44 ]. CGRP elevated the amount of Cleaved-caspase 3 and Bax and reduced the amount of Bcl-2 in human NP cells, which was a potent evidence that CGRP could induce human NP cell apoptosis in vitro.…”

Elucidation of the Key Therapeutic Targets and Potential Mechanisms of Marmesine against Knee Osteoarthritis via Network Pharmacological Analysis and Molecular Docking

“…The expression and activation of CASP3 in the monocytes, macrophages, and synovium of rheumatoid arthritis patients were measured, and treatment with the CASP3 inhibitor could effectively improve arthritis symptoms [ 31 ]. Recent study has reported that the CASP3 is a potential biomarker for OA prognosis in Egyptian donkeys [ 32 ]. Matrix metallopeptidase 9 (MMP9) has been involved in the pathological process of various diseases, including OA.…”

Exploring the Mechanism of Zanthoxylum Bungeanum Maxim in the Treatment of Osteoarthritis Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

“…Previous studies have shown that CASP3 expression is significantly increased in the chondrocytes of OA patients [50,51]. It has also been suggested that CASP3 can be used to determine the prognosis and condition of knee osteoarthritis [52]. Therefore, inhibiting the release of inflammatory factors by downregulating CASP3 expression is important for the treatment of osteoarthritis.…”