Systemic effects of severe trauma on the function and apoptosis of human skeletal cells

Abstract

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients.

Heterotopic ossification after the use of commercially available recombinant human bone morphogenetic proteins in four patients

“…Patients with cerebral trauma are susceptible to HO, and systemic levels of basic fibroblast growth factor have been shown to be elevated in these instances. 40 Eid et al 41 found that serum from polytraumatised patients significantly inhibited apoptosis in human mesenchymal bone-marrow cells, further implicating a systemic factor in the enhancement of HO.…”

Pathophysiology and Etiology of Neurogenic Heterotopic Ossification

“…The increase in bone formation seen in NHO or fracture healing in patients with TBI confirmed the activation of osteogenic cells by osteogenic factors (40). In vitro evidence showed that osteogenic factors are in the systemic circulation (10,37,(41)(42)(43)(44). An association between callus formation and osteogenic factors in serum was also shown in vivo (41).…”

“…Two studies investigating the osteogenic effect of CSF after TBI revealed that this fluid has osteogenic effect, namely, this effect has central origin (42,43). However, in these studies human tissues were rarely used and etiologic agents could not have been explained thoroughly (10,37,(41)(42)(43)(44).…”

Chiropractic Care of a Patient With Neurogenic Heterotopic Ossification of the Anterior Longitudinal Ligament After Traumatic Brain Injury: A Case Report

“…3,4 One study revealed that taking serum from polytraumatized patients and introducing it to osteoblasts and fibroblasts in vitro resulted in enhanced osteogenesis. 5 Heterotopic ossification may occur after trauma or surgery, but NHO is more prevalent in high-energy combat-related injuries of military service members. [6][7][8] Neurogenic HO is a common complication of trauma to the brain or spinal cord, and although the epidemiology is not fully understood, it can clearly be surmised that high-velocity neurotrauma greatly increases the likelihood of NHO.…”