Osteogenic protein-1 and interleukin-6 with its soluble receptor synergistically stimulate rat osteoblastic cell differentiation
✍ Scribed by Lee-Chuan C. Yeh; Michelle C. Zavala; John C. Lee
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 241 KB
- Volume
- 190
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Osteogenic Protein‐1 (OP‐1, BMP‐7), a member of the bone morphogenetic protein family, stimulates synthesis of biochemical markers characteristic of the osteoblastic and chondrocytic phenotypes and induces new bone formation. Interleukin‐6 (IL‐6), a cytokine produced by a wide variety of cells, appears to interact with other factors producing different biological effects. In the present study, we showed that OP‐1 action in fetal rat calvaria (FRC) cells was enhanced by the combination of IL‐6 and the soluble receptor IL‐6sR. OP‐1 alone induced alkaline phosphatase (AP) activity by 4‐ to 5‐fold above the control. Exogenous IL‐6 soluble receptor (IL‐6sR) synergistically stimulated the OP‐1‐induced AP activity and mineralized bone nodule formation by an additional 3‐fold. The stimulation was IL‐6sR concentration‐dependent. The combination of IL‐6 and IL‐6sR synergistically stimulated OP‐1 action by an additional 6‐ to 7‐fold. BMPR‐II receptor mRNA expression in FRC cells treated with OP‐1 and IL‐6 plus IL‐6sR was stimulated further, while BMPR‐IA, ‐IB, and ActR‐I expressions were not affected. The intracellular signaling molecules Smad2 and Smad5 mRNA expressions were not changed under these conditions. The expression of selected BMP family members (BMP‐3, ‐4, and ‐6) was altered in FRC cells treated with OP‐1 in combination with IL‐6 and IL‐6sR. The combination of IL‐6 and IL‐6sR reduced the OP‐1‐stimulated BMP‐3 mRNA levels and enhanced the suppressive effect of OP‐1 on BMP‐4 and ‐6 mRNA expressions. In conclusion, the present results demonstrate that exogenous IL‐6 and IL‐6sR synergistically stimulate OP‐1 action in primary cultures of rat osteoblastic cells. One possible mechanism of synergy involves differential regulation of the effects of OP‐1 on the expression of the type II BMP receptor and several other BMPs. J. Cell. Physiol. 190: 322–331, 2002. © 2002 Wiley‐Liss, Inc.