TGF-β With Dentalis Surface
TGF-β1 is a disulfide-bound homodimer peptide, belonging to the TGF-β family which comprises three isoforms. TGF-β1 is the most abundant isoform and it is extensively expressed in almost all tissues, in which it participates in many biological processes such as cell proliferation, differentiation, recruitment, and extracellular matrix production.
TGF-β1 exerts its signaling by binding to two types of serine-threonine kinases receptors, leading to their activation. Activated receptors phosphorylate the receptor-mediated R-Smad, Smad2/Smad3, which then form a complex with common-Smad, Smad4. The heterotrimeric complex is transported to the nucleus to regulate gene expression.
TGF-β1 is secreted by both osteoblasts and bone marrow mesenchymal stem cells (MSCs) and is stored in the bone extracellular matrix (1). The autocrine and paracrine signaling by TGF-β1 plays an important role in the maintenance and expansion of the MSCs/osteoblastic progenitor cells (2, 3) as well as the hematopoietic stem cells. Moreover, aged related reduction in TGF-β1 levels (4, 5) is suggested to be responsible for the decrease in the osteoblast progenitor cells in elderly population (6, 7).
The wide use of Titanium implants, mostly in the elderly population, motivated researchers to study TGF-β1 effects on implant osseointegration.
In human osteoblast cultures, TGF-β1 was found to stimulate differentiation, mineralization, and the formation of collagen I on Ti-6Al-4V implant surfaces
(8, 9). TGF-β1 was also shown to facilitate MSCs migration into the damaged
bone by affecting osteoclast cells (10, 11).
In osteoblasts derived from elderly human subjects, TGF-β1 was found to enhance the mineralization and the expression of bone-specific extracellular matrix proteins on implant materials (7).
At the molecular level, the central regulation of TGF-β1 induced osteoblasts differentiation is controlled by the transcription factor Runx2 and its co-activator TAZ (transcriptional coactivator with PDZ-binding motif) (12)..
The wide use of Titanium implants, mostly in the elderly population, motivated researchers to study TGF-β1 effects on implant osseointegration.
In human osteoblast cultures, TGF-β1 was found to stimulate differentiation, mineralization, and the formation of collagen I on Ti-6Al-4V implant surfaces
(8, 9). TGF-β1 was also shown to facilitate MSCs migration into the damaged
bone by affecting osteoclast cells (10, 11).
In osteoblasts derived from elderly human subjects, TGF-β1 was found to enhance the mineralization and the expression of bone-specific extracellular matrix proteins on implant materials (7).
At the molecular level, the central regulation of TGF-β1 induced osteoblasts differentiation is controlled by the transcription factor Runx2 and its co-activator TAZ (transcriptional coactivator with PDZ-binding motif) (12)..
Essentially, TGF- β1 signals result in the recruitment and maintenance of a
pool of ECM-producing cells ready for further osteoblastic differentiation by additional growth factors such as the BMPs which have synergistic effects
with TGF-β1 on osteoblast differentiation (13, 14).
Thus, TGF-β1 stimulation of migration and subsequent proliferation of osteoblasts are critical aspects of the initial steps in the cascade of new
bone tissue formation. Optimal local levels of TGF-β1 around an implant
site are suggested to serve as indicators for implant integration and
long-term fate by the maintenance of the osteoprogenitors pool
and the induction of osteoblasts differentiation.
Essentially, TGF- β1 signals result in the recruitment and maintenance of a pool of
ECM-producing cells are ready for further osteoblastic differentiation by additional growth factors such as the BMPs which have synergistic effects with TGF-β1 on osteoblast differentiation (13, 14).
Thus, TGF-β1 stimulation of migration and subsequent proliferation of osteoblasts are critical aspects of the initial steps in the cascade of new bone tissue formation.
Optimal local levels of TGF-β1 around an implant site are suggested to serve as indicators for implant integration and long-term fate by the maintenance of the osteoprogenitors pool
and the induction of osteoblasts differentiation.
Dentalis BAS surface lead to a ten-fold increase in TGF-β production, compared to the control group. These observations suggest that Dentalis surface treatment inspired by bone biology, will improve clinical performance and outcome.
The combination of innovative surface technology with 344% stronger bone reduces marginal bone loss and provides for a higher BIC%, decreasing the risk of peri-implant disease. The enhanced
deep thread simplifies the insertion and allows
for high primary stability.
The combination of innovative surface technology with 344% stronger bone reduces marginal bone loss and provides for a higher BIC%, decreasing the risk of peri-implant disease.
The enhanced deep thread simplifies the insertion and allows for high primary stability.
References
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3. Macdonald, K. K., Cheung, C. Y., and Anseth, K. S. (2007) Cellular delivery of TGFbeta1 promotes osteoinductive signalling for bone regeneration. J Tissue Eng Regen Med 1, 314-317
4. Hering, S., Isken, E., Knabbe, C., Janott, J., Jost, C., Pommer, A., Muhr, G., Schatz, H., and Pfeiffer, A. F. (2001) TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples. Exp Clin Endocrinol Diabetes 109, 217-226
5. Nicolas, V., Prewett, A., Bettica, P., Mohan, S., Finkelman, R. D., Baylink, D. J., and Farley, J. R. (1994) Age-related decreases in insulin-like growth factor-I and transforming growth factor-beta in femoral cortical bone from both men and women: implications for bone loss with aging. J Clin Endocrinol Metab 78, 1011-1016
6. Kahn, A., Gibbons, R., Perkins, S., and Gazit, D. (1995) Age-related bone loss. A hypothesis and initial assessment in mice. Clin Orthop Relat Res, 69-75
7. Zhang, H., Aronow, M. S., and Gronowicz, G. A. (2005) Transforming growth factor-beta 1 (TGF-beta1) prevents the age-dependent decrease in bone formation in human osteoblast/implant cultures. J Biomed Mater Res A 75, 98-105
8. Zhang, H., Ahmad, M., and Gronowicz, G. (2003) Effects of transforming growth factor-beta 1 (TGF-b1) on in vitro mineralization of human osteoblasts on implant materials. Biomaterials 24, 2013-2020
9. Wildemann, B., Lֳ¼bberstedt, M., Haas, N. P., Raschke, M., and Schmidmaier, G. (2004) IGF-I and TGF-beta 1 incorporated in a poly(d,l-lactide) implant coating maintain their activity over long-term storage cell culture studies on primary human osteoblast-like cells. Biomaterials 25, 3639-3644
10. Ota, K., Quint, P., Ruan, M., Pederson, L., Westendorf, J. J., Khosla, S., and Oursler, M. J. (2013) TGF-b Induces Wnt10b in Osteoclasts From Female Mice to Enhance Coupling to Osteoblasts. Endocrinology 154, 3745-3752
11. Ota, K., Quint, P., Weivoda, M. M., Ruan, M., Pederson, L., Westendorf, J. J., Khosla, S., and Oursler, M. J. (2014) Transforming Growth Factor Beta 1 induces CXCL16 and Leukemia Inhibitory Factor Expression in Osteoclasts to Modulate Migration of Osteoblast Progenitors. Bone 57, 10.1016/j.bone.2013.1007.1023
12. Zhao, L., Jiang, S., and Hantash, B. M. (2009) Transforming Growth Factor β1 Induces Osteogenic Differentiation of Murine Bone Marrow Stromal Cells. Tissue Engineering Part A 16, 725-733
13. Tachi, K., Takami, M., Sato, H., Mochizuki, A., Zhao, B., Miyamoto, Y., Tsukasaki, H., Inoue, T., Shintani, S., Koike, T., Honda, Y., Suzuki, O., Baba, K., and Kamijo, R. (2010) Enhancement of Bone Morphogenetic Protein-2-Induced Ectopic Bone Formation by Transforming Growth Factor-β1. Tissue Engineering Part A 17, 597-606
14. Singhatanadgit, W., Salih, V., and Olsen, I. (2006) Up-regulation of bone morphogenetic protein receptor IB by growth factors enhances BMP-2-induced human bone cell functions. Journal of Cellular Physiology 209, 912-922
