Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

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TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

Hedgehog and canonical Wnt/beta-catenin signaling are implicated in development of the osteoblast, the bone matrix-secreting cell of the vertebrate skeleton. We have used genetic approaches to dissect the roles of these pathways in specification of the osteoblast lineage. Previous studies indicate that Ihh signaling in the long bones is essential for initial specification of an osteoblast progenitor to a Runx2+ osteoblast precursor. We show here that this is a transient requirement, as removal of Hh responsiveness in later Runx2+, Osx1+ osteoblast precursors does not disrupt the formation of mature osteoblasts. By contrast, the removal of canonical Wnt signaling by conditional removal of the beta-catenin gene in early osteoblast progenitors or in Runx2+, Osx1+ osteoblast precursors results in a similar phenotype: osteoblasts fail to progress to a terminal osteocalcin+ fate and instead convert to a chondrocyte fate. By contrast, stabilization of beta-catenin signaling in Runx2+, Osx1+ osteoblast precursors leads to the premature differentiation of bone matrix secreting osteoblasts. These data demonstrate that commitment within the osteoblast lineage requires sequential, stage-specific, Ihh and canonical Wnt/beta-catenin signaling to promote osteogenic, and block chondrogenic, programs of cell fate specification.

/pdf/distinct-roles-for-hedgehog-and-canonical-wnt-signaling-in-49s8c1l3k4.pdf

Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors

Factors associated with the stability of titanium screws placed in the posterior region for orthodontic anchorage

Factors affecting the clinical success of screw implants used as orthodontic anchorage

Purpose: The aim of this prospective clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage. Materials and Methods: A total of 140 miniimplants in 44 patients, including 48 miniplates and 92 freestanding miniscrews, were examined in the study. A variety of orthodontic loads were applied. The majority of implants were placed in the posterior maxilla (104/140), and the next most common location was the posterior mandible (34/140). Results: A cumulative survival rate of 89% (125/140) was found by Kaplan-Meier analysis. There was no significant difference in the survival rate between miniplates and freestanding miniscrews, but miniplates were used in more hazardous situations. The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators. The estimated relative risk of implant failure in the posterior mandible was 1.101 (95% confidence interval, 0.942 to 1.301; P = .046). The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 (95% confidence interval, 0.899 to 1.405; P = .026). Discussion and Conclusion: The results confirmed the effectiveness of orthodontic mini-implants, but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates. INT J ORAL MAXILLOFAC IMPLANTS 2004;19:100‐106

Hyo-Sang Park

Papers

Factors affecting the clinical success of screw implants used as orthodontic anchorage

BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2.

Micro-implant anchorage for treatment of skeletal Class I bialveolar protrusion.

Development of orthodontic micro-implants for intraoral anchorage.

Clinical application of micro-implant anchorage.