Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through
Su Ni1,2, Ning Yi1,3, Hang Yuan1,4
1Laboratory of Clinical Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, China.
Abstract:
Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator-activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT-PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA.
Insights
Angelica Sinensis Polysaccharide (ASP) may treat osteoarthritis by activating peroxisome proliferator-activated receptor gamma (PPARγ). ASP improves mitochondrial function and reduces inflammation in chondrocytes, offering a new therapeutic approach for osteoarthritis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage wear and joint space narrowing, leading to movement disorders.
- Current understanding of OA's molecular mechanisms and effective interventions remains incomplete.
- Exploring novel therapeutic agents is crucial for managing OA progression.
Purpose of the Study:
- To investigate the potential of Angelica Sinensis Polysaccharide (ASP) in alleviating osteoarthritis (OA) progression.
- To elucidate the molecular mechanisms underlying ASP's therapeutic effects, focusing on mitochondrial metabolism and peroxisome proliferator-activated receptor gamma (PPARγ) activation.
- To evaluate the efficacy of ASP in both in vitro and in vivo models of OA.
Main Methods:
- In vitro: Assessed chondrocyte viability, apoptosis (flow cytometry), mitochondrial metabolism (ROS, MMP, cytochrome C, ATP, SOD2), and gene/protein expression (qRT-PCR, western blot) in response to tert butyl hydroperoxide (TBHP) and ASP.
- In vivo: Evaluated ASP's effects on cartilage degeneration, apoptosis (TUNEL staining), and protein expression (immunohistochemistry) in OA rat models.
- Utilized molecular pathway analysis involving PPARγ, SOD2, and ROS.
Main Results:
- ASP pretreatment activated PPARγ and SOD2 in TBHP-induced rat chondrocytes, reduced ROS, enhanced mitochondrial metabolism, improved cell viability, and decreased apoptosis.
- In vivo, ASP administration ameliorated cartilage degeneration in OA rats, promoted extracellular matrix synthesis, and slowed OA progression.
- ASP demonstrated a significant role in regulating mitochondrial metabolism in OA chondrocytes via the PPARγ/SOD2/ROS pathway.
Conclusions:
- Angelica Sinensis Polysaccharide (ASP) effectively alleviates osteoarthritis progression by activating PPARγ and improving mitochondrial function in chondrocytes.
- The therapeutic mechanism involves the PPARγ/SOD2/ROS pathway, highlighting ASP's potential in managing OA.
- ASP presents a promising novel therapeutic strategy for osteoarthritis treatment.
