Beyond Wear and Tear:

Mechanisms of Joint Degeneration, Oxidative Stress and Emerging Therapeutic Targets

Osteoarthritis is often described as a “wear and tear” condition. While mechanical loading and ageing certainly contribute to tissue changes, this characterisation overlooks the complex and ongoing biological processes that drive joint degeneration. Emerging evidence highlights the involvement of key molecular pathways, including low-grade inflammation, oxidative stress and impaired repair mechanisms, suggesting that osteoarthritis is an active, biologically mediated disease rather than a passive degenerative one.1

Going Beyond the Mechanical Paradigm

Cartilage doesn’t simply wear away as a passive consequence of joint injury. In osteoarthritis, chondrocytes – the cells responsible for maintaining cartilage – shift from a stable, homeostatic state to one that actively drives catabolic signalling within the joint. Proinflammatory cytokines stimulate the production of enzymes that degrade extracellular matrix components, accelerating the loss of collagen and proteoglycans. At the same time, low-grade synovial inflammation contributes to the onset and progression of symptoms.2 Recognising these biological drivers reframes osteoarthritis as a dynamic disease process and highlights new opportunities for targeted therapeutic intervention.

The Role of Oxidative Stress

Oxidative stress has been identified as a significant contributor to cartilage degradation. Reactive oxygen species can disrupt chondrocyte metabolism, impair mitochondrial function, and trigger lipid and protein oxidation within joint tissues. These oxidative changes may lead to apoptosis and reduce the ability of chondrocytes to maintain the extracellular matrix. An imbalance between oxidative stress and antioxidant defences contributes to progressive structural deterioration in osteoarthritis.3

Lipid oxidation products may further exacerbate joint degeneration. Once lipids are oxidised, these and other metabolites can trigger inflammatory cascades that affect both cartilage and synovial membranes. This mechanism may help explain why certain metabolic factors, such as central adiposity and dyslipidaemia, are associated with more rapid disease progression in some patients.4

Why Disease Trajectory Varies Between Patients

Osteoarthritis does not progress in the same way for everyone. Differences in inflammatory activity, joint biomechanics, metabolic stress, prior injury and tissue repair capacity all influence the course of disease. Patients with features of metabolic syndrome, elevated oxidative stress or a history of joint trauma may experience a faster rate of decline. Recognising this variability could help identify at-risk patients earlier and support more targeted interventions.

Implications for Early Intervention

This broader understanding of disease mechanisms supports an intervention model that focuses on early management of modifiable factors through the following key strategies:

Optimising weight status and metabolic health to help reduce inflammatory and oxidative burden7

Implementing exercise therapy focused on improving muscle control and joint stability

Reducing biomechanical contributors, such as joint malalignment or repetitive overload

Incorporating nutritional support aimed at mitigating inflammation and oxidative stress 5

Standardised rose-hip formulations containing the galactolipid GOPO^® have been investigated for their potential benefits in joint health. Several clinical trials have reported reductions in joint pain and improvements in function, along with decreases in inflammatory markers in some patients, suggesting an anti-inflammatory effect. 6,7 8 More recent data also support possible symptom improvements in osteoarthritis populations when used as part of a multimodal management approach.9 For certain individuals, these preparations may serve as part of a broader, multimodal management approach, particularly in the early stages of disease when inflammatory and oxidative processes may still be modifiable. 10

Translating Evidence into Practice

Supporting patients with osteoarthritis involves more than responding to established structural damage. When clinicians recognise early signs of inflammatory or oxidative activity, there is an opportunity to intervene before significant joint deterioration occurs. A combination of biomechanical management, lifestyle modification and appropriate adjunctive interventions can help preserve joint function and maintain quality of life.11

1 Riegger J, Schoppa A, Ruths L et al. (2023). Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review. Cell Mol Biol Lett. 28(1):76.

2 Ansari MY, Ahmad N, Haqqi TM. (2020). Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed Pharmacother. 129:110452.

3 Liu L, Luo P, Yang M, Wang J, Hou W, Xu P. (2022). The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review. Front Mol Biosci. 9:1001212.

4 Gu, JY, Han, F, Chen, SY et al. (2023). Research progress and hot spot analysis related to oxidative stress and osteoarthritis: a bibliometric analysis. BMC Musculoskelet Disord 24, 411.

5 Oarg? Porumb DP, Cornea-Cipcigan M, Cordea MI. (2024). Unveiling the mechanisms for the development of rosehip-based dermatological products: an updated review. Front Pharmacol. 15:1390419.

6 Winther K, Apel, K, and Thamsborg G. (2005). A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial. Scandinavian journal of rheumatology, 34(4), 302–308.

7 Winther K, Campbell-Tofte J and Hansen P. (2013). Rose Hip Powder That Contains the Natural Amount of Shells and Seeds Alleviates Pain in Osteoarthritis of the Dominant Hand - A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial. Open Journal of Rheumatology and Autoimmune Diseases, 3, 172-180.

8 Winther K, Campbell-Tofte J and Hansen P. (2013). Rose Hip Powder That Contains the Natural Amount of Shells and Seeds Alleviates Pain in Osteoarthritis of the Dominant Hand - A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial. Open Journal of Rheumatology and Autoimmune Diseases, 3, 172-180.

9 Marstrand K, Warholm L, Pedersen F et al. (2017). Dose Dependent Impact of Rose-Hip Powder in Patients Suffering From Osteoarthritis of the Hip And or Knee – A Double Blind, Randomized, Placebo Controlled, Parallel Group, Phase III Study.

10 Gruenwald J, Uebelhack R, More MI. (2019). Rosa canina - Rose hip pharmacological ingredients and molecular mechanics counteracting osteoarthritis - A systematic review. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 60, 152958.

[11] Zahan OM, Serban O, Gherman C et al. (2020). The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep. The evaluation of oxidative stress in osteoarthritis. Medicine and pharmacy reports, 93(1), 12–22.