The IL-6 family has a bad reputation for promoting inflammation, arthritis, autoimmune diseases and even cancer in the body. A recent research report published in the international journal Communications Biology titled "gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes", Scientists from the University of Southern California and other institutions have revealed the importance of IL-6 and related genes for maintaining and regenerating cartilage in joints and growth versions, which may promote bone growth and development in children.
STAT3 may be able to regulate the anabolic genes of human fetal chondrocytes and the body size of mice.
Researcher Denis Evseenko said that in this study, we found for the first time that the IL-6 family may be needed to maintain bone stem progenitor cells, and is essential for the healthy growth and function of joints and spines; previously researchers believed that in the field of skeletal muscle research, IL-6 is almost only related to arthritis, bone and muscle loss, and other chronic inflammatory diseases; and this study reveals the association between inflammation and regeneration. And hopefully helps explain why stem progenitor cells are depleted in chronic inflammatory diseases.
In the article, the researchers carefully analyzed stat3, a key gene activated by IL-6, in laboratory-grown human cells and mouse bodies, STAT3 is essential for the proliferation, survival, maturation and regeneration of chondrocyte-forming cells in joints and growth plates; when the gene stops functioning, the function of chondrogenic cells becomes worse and worse over time, resulting in smaller body size, premature fusion of growth plates, skeletal hypoplasia, and mild degeneration of articular cartilage.
When a protein called gp130 (glycoprotein 130) is lacking in the mouse body, the mice experience the same problem, all IL-6 proteins can be used to activate STAT3, and inactivating another gene called Lifr may produce similar but milder bone and cartilage changes, and the Lifr gene can encode a special protein that combines with gp130 to recognize the IL-6 protein named Lif. In mice lacking gp130, the researchers were able to restore their normal growth plates by overactivating STAT3, although this can cause overgrowth of cartilage, leading to diseases such as other bone abnormalities.
Interestingly, the researchers noticed a clear sex-related difference, when STAT3 stopped functioning, females experienced more severe cartilage and bone changes than males, and to understand why, the researchers changed estrogen levels in mouse bodies, as well as lab-grown porcine chondrocytes, in both cases, estrogen increased levels and activity of STAT3, suggesting that females may be more dependent on the gene. This study has important clinical significance for using existing drugs that inhibit STAT3 function to suppress inflammation and autoimmune diseases in the body, and these drugs may also interfere with the growth and regeneration of cartilage.
Instead, the researchers have used their understanding of the subtle differences in STAT3, the associated genes and proteins, to develop a highly targeted drug that may potentially regenerate joint cartilage without inducing inflammation, and may soon be tested in human clinical trials. Researcher Evseenko said that the results of this paper really change the current model and challenge the view that exists in the field of research, that IL-6, STAT3 and related genes and proteins not only affect inflammation, but also regeneration affects the regeneration of joint cartilage.
In summary, the results of this paper suggest that the relevant research data may describe a molecular circuit that can regulate the maintenance and output of chondrocytes, and reveal the key positive function of IL-6 family cytokines in the skeletal system, which may have a direct impact on bone development and regeneration.
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