Entry #: 46 Date: 23 April 2018
Section: Olive leaf extract (hydroxytyrosol)
Topic: Olive leaf extract and osteoarthritis
Type: In vivo model

Download PDF

OliveNetTMJournal Club

Expert review of literature related to olives and olive oil

D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Olive leaf extract prevents cartilage degeneration in osteoarthritis of SRT/ort mice


Takuma et al

Citation / Year

(1) / 2018


Olive leaf extract, hydroxytyrosol, osteoarthritis, synovial cells, cartilage, hyaluronan


Osteoarthritis is a locomotive joint disorder and represents a major clinical problem in aging. For example, the prevalence of knee osteoarthritis in the US is over 10% of people 60 years and older (2), and in Japan it is estimated that approximately 25 million people over the age of 40 years are affected by osteoarthritis (3). It is associated with a limited range of motion with pain being a key symptom, and affects the major joints (hip and knee) (4, 5). Indeed, it is the major reason for total hip and knee replacements (6). Currently, pharmacological intervention is limited, and dietary interventions and physical activity are considered important in the management of disease (7). This is of particular importance as overweight and obesity are well-recognized risk factors for osteoarthritis (7). An interesting area of research is the role of functional foods, and in this context, glucosamine, chondroitin sulphate, hydrolysed collagen, and other herbs and nutrients have been considered (8-10). Further, olive oil has been shown to have beneficial effects in rheumatoid arthritis in human trials (12 week administration) (10), and olive leaf extract and specific olive phenolics, particularly hydroxytyrosol, have been shown to have beneficial effects in relevant animal models of disease (11). This study aimed to extend our understanding of olive-related beneficial effects in osteoarthritis using a well-established animal model of disease (12). Specifically, the STR/ort model in which mice develop age-related spontaneous osteoarthritis of the medial tibial cartilage, similar to human disease was utilised (13).

Key points and implications

This study utilised both male and female STR/ort mice, and aging mice (28 weeks old), were used for experiments. The overall aim was to examine the effects of olive leaf extract (containing 20% hydroxytyrosol), in the development of osteoarthritis in the animals. Following, oral administration of olive leaf extract for eight weeks, conventional experiments including, analysis of gait (using available GAIT® software, Noveltec, Inc.), histological analysis of articular cartilage, and measurement of serum levels of type II collagen, were performed. The findings indicated slight improvements (although not statistically significant a definite trend) in gait analysis, histological parameters, and a slight increase in type II collagen in olive leaf extract treated mice, compared to the osteoarthritis control group. As an extension, cell culture studies were performed in HIG-82 synovial cells. Cells were treated with olive leaf extract and effects on hyaluronan were examined. The findings indicated an increase in concentration of hyaluronan peaking after treatment with a concentration of 0.1 μg/mL olive leaf extract for 18 hours. Agarose gel electrophoresis indicated that olive leaf extract stimulated the expression of high molecular weight hyaluronan. Overall, these findings highlight that treatment of mice with a continual administration of olive leaf extract, particularly at the onset of disease, can attenuate the progression of osteoarthritis. Importantly, the findings indicate that olive-related compounds may enhance the lubricating effect of synovial fluid by increasing the expression of high molecular weight hyaluronan in synovial cells. These findings provide the basis for further investigation in this important field of research.

Related publications

  1. M. Takuma et al., Olive leaf extract prevents cartilage degeneration in osteoarthritis of STR/ort mice. Bioscience, biotechnology, and biochemistry, 1-6 (2018).
  2. Y. Zhang, J. M. Jordan, Epidemiology of osteoarthritis. Clinics in geriatric medicine 26, 355-369 (2010).
  3. N. Yoshimura et al., Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women: the research on osteoarthritis/osteoporosis against disability study. Journal of bone and mineral metabolism 27, 620-628 (2009).
  4. N. M. Hadler, Knee pain is the malady–not osteoarthritis. Annals of internal medicine 116, 598-599 (1992).
  5. A. A. Guccione et al., The effects of specific medical conditions on the functional limitations of elders in the Framingham Study. American journal of public health 84, 351-358 (1994).
  6. C. J. DeFrances, M. N. Podgornik, 2004 National Hospital Discharge Survey. Advance data, 1-19 (2006).
  7. D. T. Felson et al., Osteoarthritis: new insights. Part 1: the disease and its risk factors. Annals of internal medicine 133, 635-646 (2000).
  8. D. O. Clegg et al., Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. The New England journal of medicine 354, 795-808 (2006).
  9. J. Ezaki, M. Hashimoto, Y. Hosokawa, Y. Ishimi, Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model. Journal of bone and mineral metabolism 31, 16-25 (2013).
  10. A. A. Berbert, C. R. Kondo, C. L. Almendra, T. Matsuo, I. Dichi, Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 21, 131-136 (2005).
  11. L. Wang et al., The anti-atherosclerotic effect of olive leaf extract is related to suppressed inflammatory response in rabbits with experimental atherosclerosis. European journal of nutrition 47, 235-243 (2008).
  12. K. A. Staines, B. Poulet, D. N. Wentworth, A. A. Pitsillides, The STR/ort mouse model of spontaneous osteoarthritis – an update. Osteoarthritis and cartilage 25, 802-808 (2017).
  13. R. M. Mason et al., The STR/ort mouse and its use as a model of osteoarthritis. Osteoarthritis and cartilage 9, 85-91 (2001).