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Skin & Muscle

New Collagen Therapy Can Treat Arthritis and Regenerate Joints, Turkish Study Reveals

Researchers show that structurally intact (undenatured) collagen protein helps restore joint health in young and aged female rats with osteoarthritis.

By Dylan G. Arrazati

Key Points: 

  • Treating young and aged rats modeling osteoarthritis (OA) – joint degradation – with undenatured collagen improves joint health and mitigates features of OA, particularly inflammation. 

Osteoarthritis prevalence has risen by an astounding 48% since 1990,  affecting more than 500 million people across the globe.  And while the majority of individuals succumbing to this deteriorating disease are elderly individuals, new evidence indicates that younger people are experiencing OA at higher rates due to obesity, joint trauma, and sports-related injuries. Thus, researchers have focused on identifying OA interventions that work across multiple age groups. 

In a new study published in Scientific Reports, Turkish researchers examined the effects of undenatured collagen gently isolated from chicken sternum cartilage in young and old rats modeling OA. The investigators found that supplementing this patented form of collagen to young and old rats improved locomotor function and reduced  Kellgren-Lawrence scores –  a measurement for the severity of knee OA. What’s more,  treatment attenuated Mankin scores- a measurement for cartilage erosion and cartilage structural arrangement. Notably, the findings showed that undenatured collagen (UC) supplementation reduced markers of inflammation and joint cartilage breakdown while increasing the activity of antioxidants. 

Understanding Joint Aging and The Role of Undenatured Collagen 

The integrity and resilience of our joints heavily rely on healthy collagen (a protein that composes connective tissue) and extracellular matrix proteins, which provide structural and biochemical support to cells within tissues and organs.  The cells that produce these two vital joint components are known as chondrocytes, which studies have shown are primary targets in people with OA. Moreover,  scientists have found that age-related increases in inflammation and reactive oxygen species (ROS) – compounds that contribute to oxidative stress – compromise chondrocyte health, ultimately exacerbating joint deterioration and cartilage degradation. 

What makes UC unique is its ability to trigger oral tolerance, an intricate biological process that induces joint cartilage repair by increasing anti-inflammatory molecules. Accordingly, elevating anti-inflammatory activity in joint tissue generates the articular cartilage matrix, the primary component of articular cartilage – connective tissue that spans the surface of joints and bones. Previous studies have established UC as an effective tool to mitigate the effects of OA. However, until now, no one had examined the effects of varying dosages of UC in both young and aged subjects. 

Undenatured Collagen Preserves Motor Function and Ameliorates OA

Sahin and colleagues supplemented young (2-month-old) and aged (18-month-old) rats  modeling OA with one of the following doses of undenatured collagen for 37 days: 0.66 mg/kg, 1.33 mg/kg, or 2 mg/kg. Then, the investigators conducted gait tests to look for locomotor abnormalities following treatment. After 37 days of treatment, the results showed that aged rats responded extremely well to all doses of UC, with all gait measurements showing improvements.  However, gait improvements in young rats only reached statistical significance with the two higher dosages of undenatured collagen. 

The research team also quantified Kellgren-Lawrence scores (scale: 0-4), with higher scores indicating worse knee OA.  In both age groups,  untreated rats displayed a score of three, but the investigators found that all doses of undenatured collagen effectively lowered scores to approximately one in young rats.  On the other hand, aged rats only achieved a score of one with 1.33 and 2 mg/kg of UC.  Notably, rats in both age groups treated with 2 mg/kg displayed the least amount of knee swelling

Similar results were after calculating Mankin scores, with higher scores representing more severe cartilage damage. The two highest UC dosages significantly reduced Mankin scores in both age groups, with the 2 mg/kg treatment outperforming the rest. Also, rats treated with 2 mg/kg of UC exhibited less cartilage erosion than rats treated with lower UC dosages. Altogether,  the findings demonstrate that a higher dosage of UC is the most effective at alleviating knee OA. 

(Sahin et al., 2023 | Scientific Reports) UC treatment increases stride length and reduces both Kellgren-Lawrence and Mankin scores. (Left) Aged OA rats treated with 0.66 (green), 1.33 (purple), or 2 (orange) mg/kg UC have longer strides than untreated rats (MIA), indicative of improved gait measurements. Aged OA rats treated with 2 mg/kg of UC have the lowest Kellgren-Lawrence (middle) and Mankin (right) scores. 

Undenatured Collagen Ameliorates Joint Inflammation

Sahin and colleagues proceeded to compare the anti-inflammatory effects of each UC dosage to further elucidate the oral tolerance mechanism. Given that aging exacerbates inflammation, the investigators posited that aged rats would need a higher UC dosage to achieve oral tolerance. The results showed that all dosages of UC reduced markers of inflammation (IL6, IL-1b) and increased the activity TGF-β – a powerful anti-inflammatory molecule – in young and aged rats. 

UC’s effect on inflammation was dose-dependent in aged rats, confirming that a higher UC dosage is needed to achieve oral tolerance later in life. However, young rats still achieved oral tolerance with 0.66 mg/kg of UC, meaning that younger individuals may not need as much UC to preserve joint health. Collectively, the findings suggest that UC can restore oral tolerance across multiple age groups but at varying dosages.

(Sahin et al., 2023 | Scientific Reports) UC treatment mitigates inflammation. Young and aged OA rats treated with 0.66 (MIA+UC 0.66), 1.33 (MIA+UC 1.33), or 2 (MIA+UC 2) mg/kg of UC have lower il-6 levels and higher TGF-β levels than untreated rats (MIA). 

Taking Undenatured Collagen to Take Charge of Joint Aging

In addition to establishing the beneficial effects of UC on OA at varying doses, the Turkish research team also demonstrates the safety of UC injection in young and aged subjects, with no severe adverse effects reported. This study is also one of the first to show that young individuals experiencing early onset OA can potentially utilize UC to delay joint aging. Oral UC supplements already exist in the market, but it’s important to highlight that taking UC orally instead of through injection could potentially produce different results than those seen in this study. Remember to always consult with a doctor before starting any kind of supplementation. 

Model & Dosage

Model: young (2-month-old) and aged (18-month-old) female rats

Dosage: undenatured collagen for 37 days via intraarticular injection: 0.66 mg/kg, 1.33 mg/kg, or 2 mg/kg

Source

Sahin, E., Orhan, C., Erten, F. et al. The effect of oral administration of undenatured type II collagen on monosodium iodoacetate-induced osteoarthritis in young and old rats. Sci Rep 13, 6499 (2023). https://doi.org/10.1038/s41598-023-33763-2

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