[Free Full Text] Polyphenols on chondrocyte growth and survival

The impact of polyphenols on chondrocyte growth and survival: a preliminary report,  © 2015 Salvador Fernández-Arroyo et al., Food & Nutrition Research 2015, 59: 29311

"Imbalances in the functional binding of fibroblast growth factors (FGFs) to their receptors (FGFRs) have consequences for cell proliferation and differentiation that in chondrocytes may lead to degraded cartilage. The toxic, proinflammatory, and oxidative response of cytokines and FGFs can be mitigated by dietary polyphenols."

Jesus Pintor's research team explored what the  possible effects of polyphenols in the management of osteoarticular diseases are using a model based on the transduction of a mutated human FGFR3 (G380R) in murine chondrocytes. This mutation is present in most cases of skeletal dysplasia and is responsible for the overexpression of FGFR3 that, in the presence of its ligand, FGF9, results in toxic effects leading to altered cellular growth.

Well, what does this mean? What are polyphenols in the first place?

Polyphenols are naturally occurring compounds found largely in fruits, vegetables, cereals and beverages. Fruits like grapes, apple, pear, cherries and berries contains up to 200-300 mg polyphenols per 100 grams fresh weight. The products manufactured from these fruits, also contain polyphenols in significant amounts. Typically a glass of red wine or a cup of tea or coffee contains about 100 mg polyphenols. Cereals, dry legumes and chocolate also contribute to the polyphenolic intake. In Plant polyphenols as dietary antioxidants in human health and disease, Pandey, K., Rizvi,S. 2009

Polyphenols have  antioxidant and anti-inflammatory properties with a synergistic impact in metabolic functions and maintenance of cellular homeostasis. So, what is an antioxidant?

"An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation is a chemical reaction involving the loss of electrons which can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid (vitamin C), or polyphenols". Further reading here.

Achondroplasia is due to a mutation that increases the activity of FGFR3, the fibroblast growth factor receptor 3, in the external membrane of the  chondrocytes (located in the growth plate of the long bones).

In this article by Jesus Pintor, the team says that "Dietary polyphenols are probable candidates to modulate and regulate disturbances, among others in rat sarcoma protein/mitogen activated protein kinase (RAS/MAPK [ERK-1/-2]). The cascade that also occurs in chondrocytes.

And "because  dietary polyphenols block the actions of some cytokines (that activate inflamation) and FGFs that lead to cartilage degradation" this team "tested the hypothesis that dietary polyphenols might have an important regulatory effect on the functional binding of FGFs to their receptors".

This work is a speculative approach, but science works this way! Testing new hypothesis and going for different approaches.

The extract of polyphenol used in this experiment was from Hibiscus sabdariffa (family Malvaceae; karkadé). They studied the effects of H. sabdariffa extract and concentrated polyphenols in cartilage matrix deposition in chondrocytes.

Hibiscus Sabdariffa can be  taken as a tea (Roselle or Sour Tea). The usually dark colored flowers are used to brew. It appears to inhibit carbohydrate absorption to a degree and appears to be effective in reducing blood pressure.

Conclusions

This is indeed, the most difficult part of this study. The conclusions are inconsistent and vague, needing further research. The research team concluded that:

1. Most polyphenols had no effect, but those provided by H. sabdariffa rescued chondrocytes from FGF9-induced toxic effects, supporting the view that plant-derived dietary products affect intracellular signaling networks and may be safely utilized in the management of degraded cartilage phenotypes.


2. H. sabdariffa rescued mutated FGFR3 chondrocytes, restoring normal growth, decreasing the intracellular chloride concentration, inhibiting ERK-1/-2 phosphorylation, and increasing the generation of ECM.


3. Polyphenols appeared to be the compounds causing the inhibition of ERK-1/-2 (p42 and p44) phosphorylation.


4. Total values were lower than those observed in wild type cells, indicating the probable contribution of other mechanisms.


5. Interpretation is difficult because data could indicate combined actions on FGFR3 signaling, binding of FGF9, or direct preservation of the membrane potential.


6. Results suggest that these bioactive compounds (from Hibiscus) are not affecting the receptor directly (FGFR3)


7. Exploration of related signaling pathways other than ERK-1/-2 in chondrocytes and the effect of some available drugs might also contribute to fully uncovering the actual molecular mechanisms.

Nevertheless, I agree that it is a good time to "contemplate significant dietary modifications in humans by food design and supplementation to obtain health benefits".