Results
Long-term dietary PQQ markedly reduced spontaneous, age-related osteoarthritis in mice as measured by OARSI scoring.
- Twelve-month-old mice received dietary PQQ at 4 mg/kg feed for 12 months
- Joint pathology was assessed by Safranin O-Fast Green staining and OARSI grading
- PQQ lowered OARSI scores compared to untreated aged mice
- PQQ reduced osteophyte formation and synovitis scores
Results
PQQ preserved cartilage and subchondral bone structure in aged mice.
- Structural assessment was performed using micro-computed tomography (μCT)
- Safranin O-Fast Green staining confirmed cartilage preservation
- Both osteophyte formation and synovitis were reduced with PQQ treatment
- Subchondral bone structural integrity was maintained in PQQ-treated mice
Results
PQQ decreased oxidative DNA damage and reduced cellular senescence markers in cartilage of aged mice.
- PQQ decreased oxidative DNA damage in cartilage tissue
- Senescence markers were reduced in PQQ-treated mice
- Senescence-associated secretory phenotype (SASP) factors were diminished
- Lamin B1, a marker of cellular senescence, was restored by PQQ treatment
Results
PQQ reduced matrix degradation markers and maintained extracellular matrix protein expression in aged mouse cartilage.
- PQQ reduced matrix metalloproteinase-13 (MMP13) expression
- COL2A1 (type II collagen) expression was maintained with PQQ treatment
- These effects indicate preservation of extracellular matrix integrity in cartilage
Results
In IL-1β-challenged human chondrocytes and cartilage explants, PQQ suppressed oxidative stress, rescued proliferation, diminished senescence, and prevented matrix degradation.
- Human and mouse chondrocytes and cartilage explants were treated with interleukin-1β (IL-1β) to model OA in vitro
- PQQ suppressed oxidative stress in IL-1β-challenged chondrocytes
- PQQ rescued proliferation that was diminished by IL-1β treatment
- Matrix degradation was prevented by PQQ in this in vitro OA model
Results
PQQ enhanced Nrf2 nuclear accumulation, antioxidant response element (ARE) activity, and antioxidant gene expression in chondrocytes.
- PQQ promoted nuclear accumulation of Nrf2 transcription factor
- ARE activity was enhanced following PQQ treatment
- Antioxidant gene expression was upregulated downstream of Nrf2 activation
- Nrf2 is described as a transcription factor that regulates antioxidant and cytoprotective gene expression
Results
IGF1R was identified as a direct transcriptional target of Nrf2 in chondrocytes.
- Mechanistic assays identified IGF1R as a direct Nrf2 target gene
- This represents a novel mechanistic link between Nrf2 signaling and IGF1R expression in cartilage
- IGF1R knockdown blocked PQQ-induced ERK (extracellular signal-regulated kinase) signaling
- IGF1R knockdown also blocked PQQ-induced COL2A1 upregulation
Results
PQQ failed to protect Nrf2-deficient chondrocytes and joints, demonstrating that PQQ's protective effects are Nrf2-dependent.
- Nrf2 loss-of-function experiments were performed to evaluate pathway dependence
- Chondrocytes lacking Nrf2 were not protected by PQQ treatment
- Joint protection by PQQ was abolished in Nrf2-deficient conditions
- IGF1R loss-of-function was also used to evaluate pathway dependence downstream of Nrf2
Background
Age-related knee osteoarthritis arises from cumulative oxidative damage, chondrocyte senescence, and extracellular matrix loss, and safe disease-modifying interventions for aging-associated OA are lacking.
- PQQ has molecular formula C14H6N2O8 and is described as a naturally bioactive compound
- PQQ has been previously reported to activate Nrf2
- Prior to this study, effects of PQQ on age-related OA and underlying mechanisms remained unclear
- The study used 12-month-old mice treated for 12 months, representing a long-term aging model