Vías de señalización anabólicas en el hueso y su potencial aplicación en la terapéutica
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Palabras clave

osteoporosis
esclerostina
DKK1
anabólico óseo
Sclerostin
osteo-anabolic

Cómo citar

Sierra, A., Medina, A., Rojas, W., Tovar, H., Révérend, C., & Suárez, A. (2017). Vías de señalización anabólicas en el hueso y su potencial aplicación en la terapéutica. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 1(1), 12–19. https://doi.org/10.53853/encr.1.1.56

Resumen

Para el manejo actual de la osteoporosis contamos con la terapia antirresortiva, que estabiliza la arquitectura ósea sin lograr su restauración y la anabólica (teriparatida: único aprobado por la FDA) que restaura y aumenta la masa ósea. La identificación de reguladores moleculares con efecto anabólico sobre el hueso ha permitido el desarrollo de nuevas terapias para el manejo de esta patología cada vez más prevalente.
La vía de señalización Wnt/?-catenina aumenta la masa ósea a través de la diferenciación de células mesenquimales hacia osteoblastos y mediante el estímulo de la replicación de preosteoblastos e inhibición de la apoptosis de osteoblastos y osteocitos, siendo las proteínas esclerostina y DKK1 (Dickko- pf 1) sus principales antagonistas. Se encuentran actualmente en desarrollo anticuerpos monoclonales humanizados contra estas proteínas (Ac anti esclerostina y anti DDK1) que tienen a un efecto formador de hueso.
Otra alternativa de uso local es la Proteína Morfogénica de Hueso 2, recombinante humana (rhBMP-2), con capacidad osteogénica, que ha demostrado aumentar la resistencia ósea en zonas de fracturas, acelerando la consolidación de las mismas.
Estos nuevos reguladores del remodelado óseo representan una alternativa terapéutica de la osteoporosis y otros trastornos asociados al desequilibrio entre la resorción y la formación ósea.

Summary
The current management of osteoporosis includes antiresorptive therapy, which stabilizes bone architecture without achieving its restoration, and anabolic therapy (Teriparatide: the only agent approved thus far by the FDA), which restores and increases bone mass. The identification of molecular regulators with anabolic effect on bone has allowed for developing new therapies for the management of this increasingly prevalent condition.
The Wnt/?-catenin signaling pathway increases bone mass via differentiation of mesenchymal cells into osteoblasts, stimulation of pre-osteoblasts replication and inhibition of the apoptosis of osteoblasts and osteocytes, with the proteins Sclerostin and DKK1 (Dickkopf 1) being its main antagonists. Humanized monoclonal antibodies against these proteins (anti-sclerostin and anti-DDK1 Ab), which have bone forming effects, are currently being developed.
Another alternative is the local use of human recombinant bone morphogenetic protein 2, (rhBMP-2), a protein with osteogenic capacity, which has been shown to increase bone strength at fracture areas, accelerating their consolidation.
These new bone remodeling regulators represent a therapeutic alternative for osteoporosis and other disorders associated with an imbalance between bone resorption and formation.

https://doi.org/10.53853/encr.1.1.56
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Citas

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