Davis Lab Research Projects

Characterization of Perineurial Cells Involved in BMP2-induced HO

It is known that the tumor microenvironment can contain regulatory T cells and myeloid derived suppressor cells, which help tumors evade immune surveillance mechanisms and grow. After repeated analysis of heterotopic ossification (HO), we now believe that the process of heterotopic ossification could be similar to that of tumor development, also with its own unique microenvironment and system for evading immune system surveillance. We’ve recently discovered a population of macrophages present in the lesional area of HO and are attempting to characterize them, determine their origin, and discover their role in HO. Such a task is important as the determination of how individual components of the immune system interact with the bone formation process is a crucial step for advancing orthopedic injury repair.

Chemical Suppression of Neuroma Formation and Associated Effect on HO

Our previous studies have demonstrated the role of neuroinflammation in BMP2-induced HO. Part of this process is the activation of β3- adrenergic receptor-expressing cells in the perineurium of the peripheral nerves, which causes their replication, mitochondrial expansion, and subsequent formation of a peripheral nerve neuroma.

This current project has identified a few potential drug candidates for the inhibition of this process by blocking either the activation of β3- adrenergic receptor or by interfering with other stages like mast cell degranulation.

Our lab is currently investigating how the suppression of this neuroinflammatory process affects the bone formation typically achieved in our model of BMP2-induced HO.

Role of Peripheral Nerve Injury and Blood-nerve Barrier in HO

Our lab’s previous studies have demonstrated that osteogenic progenitors that contribute to HO are housed in the endoneurium in a mouse model. The results of our studies in larger animals such as rats have indicated that a similar model to induce bone with BMP2-producing cells does not produce the same results.

We have hypothesized that this could be due to the more sophisticated peripheral nervous system in higher order species, which possess multi-fascicled nerves and a complex blood-nerve barrier.

We are currently testing whether a mechanical or chemical opening of this barrier contributes to the formation of bone in BMP2-induced neurogenic HO.