The role of small molecules in musculoskeletal regeneration

Written by Regenerative Medicine

In this review from researchers at Institute for Regenerative Engineering, University of Connecticut Health Center (CT, USA), published in Regenerative Medicine, learn more about the development of small molecules that can with the ability to induce osteoblastic differentiation.

The uses of bone morphogenetic proteins and parathyroid hormone therapeutics are fraught with several fundamental problems, such as cost, protein stability, immunogenicity, contamination and supraphysiological dosage. These downsides may effectively limit their more universal use. Therefore, there is a clear need for alternative forms of biofactors to obviate the drawbacks of protein-based inductive factors for bone repair and regeneration.

Small molecules with the capacity to regulate osteoblast differentiation and mineralization could offer an alternative, as their inherent physical properties minimize limitations observed in protein growth factors. For instance, in general, small molecule inducers are usually more stable, highly soluble, nonimmunogenic, more affordable and require lower dosages. Small molecules with the ability to induce osteoblastic differentiation may represent the next generation of bone regenerative medicine. 

Figure 1. Different forms of bone growth factors involved in osteoblast differentiation. (A) The protein ligand interacts with the extracellular domain of the membrane receptor, and in turn the intracellular domain of the receptor activates the target signal cascade. (B) The small molecules pass through the cell membrane and directly activate the intracellular target signaling cascade. Activation of the signaling cascade will lead to modification of the transcription factor. The modified transcription factor will then translocate from the cytoplasm to the nucleus and induce the expression of the osteoblast-associated gene.

In this review, originally published in Regenerative Medicine, learn more about efforts to develop small molecule-based biofactors for induction, paying specific attention to their novel roles in bone regeneration.

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