Sunday, September 12, 2010


IL-10 is also known as TGIF and IL10 interacts with Retinoic Acid and TGFBeta3.

Role of Interleukin-10 in endochondral bone formation: Anabolic effect via BMP/Smad pathway.

"Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with a chondroprotective effect that is elevated in cartilage and synovium in osteoarthritis. Loss and gain of IL-10 functions during endochondral bone formation were studied using IL-10 null mice and IL-10-treated tibia organ cultures, respectively. Primary chondrocytes from the long bones of embryo were cultured with or without IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted mesenchymal cell micromass culture. Results. Whole skeletal lengths of IL-10 null mice were similar to those of wild type littermates, although skull diameters were smaller. The growth plates of tibia of IL-10 null mice showed shortening of the proliferating zone. Treatment with IL-10 significantly increased tibial lengths in organ culture. IL-10 induced chondrocyte proliferation and hypertrophic differentiation in primary chondrocytes in vitro. Mechanistically, IL-10 activated Stat3 and the Smad1/5/8 and Erk1/2 MAP kinase pathways{LSJL activates Smad1/5/8 and ERK1/2 pathway}, and induced the expression of BMP2 and BMP6 in primary chondrocytes. Furthermore, the blocking of BMP signaling attenuated the IL-10-mediated induction of cyclin D1, and Runx2 in primary chondrocytes, and suppressed alcian blue and alkaline phosphatase staining in mesenchymal cell micromass culture.  IL-10 acts as a stimulator of chondrocyte proliferation and chondrogenic or hypertrophic differentiation via activation of BMP signaling pathway."

"The initial response of chondrocytes to external mechanical loading is adaptation, that is, they become metabolically active and proliferative. However, repetitive stress induces hypertrophic differentiation and eventually chondrocyte apoptosis. During this process, the balance between anabolic and catabolic signaling pathways in which Sox9 and Runx2, respectively, function
as major regulatory transcription factors is critical in the determination of the fate of chondrocytes"

"In addition to mature chondrocytes, mesenchymal stem cells (MSCs) and MSCs differentiated along the chondrogenic lineage express substantial amounts of IL-10"

"IL-10 promotes the production of extracellular matrix proteins of cartilage, such as, type II collagen, and aggrecan"

"Other signaling pathways, including Akt and IkB, were not activated by IL-10."<-LSJL activates the Akt pathway.

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