Heterotopic Ossification Has Some Nerve (original) (raw)
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Trauma-Induced Heterotopic Ossification Regulates the Blood-Nerve Barrier
Frontiers in neurology, 2018
bone formation can occur in soft tissues as a result of traumatic injury. This process, known as heterotopic ossification (HO), has recently been linked to the peripheral nervous system. Studies suggest that HO may resemble neural crest-derived bone formation and is activated through the release of key bone matrix proteins leading to opening of the blood-nerve barrier (BNB). One of the first steps in this process is the activation of a neuro-inflammatory cascade, which results in migration of chondro-osseous progenitors, and other cells from both the endoneurial and perineurial regions of the peripheral nerves. The perineurial cells undergo brown adipogenesis, to form essential support cells, which regulate expression and activation of matrix metallopeptidase 9 (MMP9) an essential regulatory protein involved in opening the BNB. However, recent studies suggest that, in mice, a key bone matrix protein, bone morphogenetic protein 2 (BMP2) is able to immediately cross the BNB to activat...
Bone, 2017
Heterotopic ossification (HO), or de novo bone formation in soft tissue, is often observed following traumatic injury. Recent studies suggest that peripheral nerves may play a key functional role in this process. The results supporting a neurological basis for HO are examined in this article. Evidence supports the fact that BMPs released from bone matrix possess the capacity to induce HO. However, the process cannot be recapitulated using recombinant proteins without extremely high doses suggesting other components are required for this process. Study of injuries that increase risk for HO, i.e. amputation, hip replacement, elbow fracture, burn, and CNS injury suggests that a likely candidate is traumatic injury of adjacent peripheral nerves. Recent studies suggest neuroinflammation may play a key functional role, by its ability to open the blood-nerve barrier (BNB). Barrier opening is characterized by a change in permeability and is experimentally assessed by the ability of Evans bl...
Progenitors in Peripheral Nerves Launch Heterotopic Ossification
Stem cells translational medicine, 2017
Studies presented here, using a murine model of bone morphogenetic protein type 2 (BMP2)-induced heterotopic ossification (HO) show that the protein initiates HO by signaling through progenitors in the endoneurium of peripheral nerves. In the mouse, these cells were identified in the endoneurium one day after BMP2 induction using antibody against phosphoSMAD (PS) 1, 5, and 8. Studies conducted in a tracking mouse that contains a tamoxifen-regulated Wnt1-Cre recombinase crossed with a td Tomato red (TR) reporter (Wnt1(CreErt) :Ai9Tm) confirmed their neural origin. In this model both BMP2 induction and tamoxifen are absolutely required to induce TR. SP7(+) (osterix(+) )TR(+) cells were found in the endoneurium on day 1 and associated with bone on day 7. Quantification of TR(+) and TR(-) cells isolated by fluorescence-activated cell sorting showed that all SP7(+) cells were found in the TR(+) population, whereas only about 80% of the TR(+) cells expressed SP7. Pre-chondrocytes (Sox 9(+...