Transforming growth factor-β3 (Tgf-β3) down-regulates Tgf-β receptor type I (Tβr-I) during rescue of cranial sutures from osseous obliteration

• Published in: Orthodontics & craniofacial research Vol. 5; no. 1; pp. 5 - 16
• Main Authors: Opperman, LA, Galanis, V, Williams, AR, Adab, K
• Format: Journal Article
• Language: English
• Published: Oxford UK Munksgaard International Publishers 01.02.2002
• Subjects: cranial sutures; craniosynostosis; intramembranous bone; morphogenesis; Tgf-β receptors
• ISSN: 1601-6335; 1601-6343
• DOI: 10.1034/j.1600-0544.2002.01179.x

Appropriate biochemical regulation of intramembranous bone growth from sutures is necessary to achieve correct craniofacial morphology. Failure to form sutures (agenesis) or to maintain sutures in their unossified state (craniosynostosis) can result in severe facial dysmorphology. Several factors such as Twist, Msx2, fibroblast growth factors (Fgfs), bone morphogenetic proteins (Bmps) and transforming growth factors‐β (Tgf‐βs) regulate suture patency, likely by interacting with one another. Tgf‐β2 and Tgf‐β3 use the same cell surface receptors, yet have opposite effects on suture patency, cellular proliferation and apoptosis within the suture. One possible mechanism by which Tgf‐β3 rescues sutures from obliteration is by regulating the ability of suture cells to respond to Tgf‐β2. As Tgf‐β3 does not regulate protein levels of Tgf‐β2 in sutures, Tgf‐β3 could regulate tissue responsiveness to Tgf‐β2 by regulating Tgf‐β2 access to receptors. Tgf‐β3 is a more potent competitor than Tgf‐β2 for cell surface receptors, so it is proposed that Tgf‐β3 binds to and down‐regulates Tgf‐β receptor type I (Tβr‐I) expression by suture cells. This down‐regulation would limit the ability of cells to respond to all Tgf‐βs, including Tgf‐β2. To test this hypothesis, an in vitro culture model was used in which fetal rat sutures either remain patent or are induced to fuse when cultured in the presence or absence of dura mater, respectively. Tgf‐β3 was added to cultured calvaria and changes in the number of receptor positive cells within the suture were established. Data were compared with that seen in control sutures and in normal sutures in vivo. It was found that the numbers of cells expressing Tβr‐I within the suture matrix increased over time in sutures remaining patent. Osteoblastic cells lining the bone fronts on either side of sutures were Tβr‐I positive during early morphogenesis, but these numbers declined as sutures fused, both in vivo and in vitro. Addition of Tgf‐β3 to calvaria in culture decreased the number of Tβr‐I expressing cells in both fusing and non‐fusing sutures, with dramatic decreases in the numbers of osteoblasts expressing Tβr‐I.