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Transforming Growth Factor-β1 Stimulates Chondrogenic Differentiation of Posterofrontal Suture–Derived Mesenchymal Cells In Vitro

Xu, Yue M.D., Ph.D.; James, Aaron W. B.A.; Longaker, Michael T. M.D., M.B.A.

Plastic and Reconstructive Surgery: December 2008 - Volume 122 - Issue 6 - p 1649-1659
doi: 10.1097/PRS.0b013e31818cbf44
Experimental: Original Articles

Background: Evidence from animal studies has associated transforming growth factor (TGF)-β signaling with both normal and premature cranial suture fusion. However, the mechanisms whereby this pleiotropic cytokine mediates suture fusion remain uncertain. The authors established cultures of suture-derived mesenchymal cells from normally fusing (posterofrontal) and patent (sagittal) sutures and examined the in vitro effects of TGF-β1 on these distinct cell populations.

Methods: Skulls were harvested from 80 5-day-old mice. Posterofrontal and sagittal sutures were dissected, and cultures of suture-derived mesenchymal cells were established. The mitogenic, osteogenic, and chondrogenic effects of recombinant TGF-β1 were then assessed on posterofrontal and sagittal suture–derived mesenchymal cells (1 to 10 ng/ml). Quantitative real-time polymerase chain reaction was used to examine the effects of TGF-β1 on gene expression.

Results: TGF-β1 significantly decreased proliferation of both posterofrontal and sagittal suture–derived mesenchymal cells, by bromodeoxyuridine incorporation assays (n = 6). TGF-β1 also inhibited osteogenesis in both suture-derived mesenchymal cells determined by alkaline phosphatase activity and mineralization (n = 3 for all assays). During chondrogenic differentiation, TGF-β1 markedly increased expression of chondrocyte-specific gene markers in posterofrontal suture–derived mesenchymal cells (Sox9, Col II, Aggrecan, and Col X) (p ≤ 0.05). In contrast, TGF-β1 did not increase chondrocyte-specific gene expression in sagittal suture–derived mesenchymal cells (n = 3).

Conclusions: Posterofrontal suture–derived mesenchymal cells retain significant capability for both osteogenic and chondrogenic differentiation in vitro. TGF-β1 induces in vitro chondrogenesis in posterofrontal but not sagittal suture–derived mesenchymal cells. Future studies will focus on elucidating the mechanisms whereby TGF-β signaling mediates chondrogenesis in posterofrontal suture–derived mesenchymal cells.

Stanford, Calif.

From the Hagey Pediatric Regenerative Research Laboratory and the Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine.

Received for publication March 12, 2008; accepted May 23, 2008.

The first two authors share first authorship of this article.

Disclosure: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

Michael T. Longaker, M.D., M.B.A. Hagey Pediatric Regenerative Research Laboratory; Stanford University School of Medicine; Stanford University; 257 Campus Drive; Stanford, Calif. 94305-5148;

©2008American Society of Plastic Surgeons