Mathematical model of bone morphogenetic proteins’ influence on intervertebral disc cell proliferation in vitro

Bone morphogenetic proteins change the cellular expression of extracellular matrix components. In the early stages of intervertebral disc degeneration this can be the basis for biological treatments intending to regenerate the structure and function of the intervertebral disc. The success of this therapy depends on the presence of a sufficient number of viable cells. The study was aimed to investigate the proliferation of intervertebral disc cells under the influence of bone morphogenetic proteins. Healthy human annulus fibrosus and nucleus pulposus cells were cultured in control medium (1), and medium supplemented with bone morphogenetic protein-2 (2), bone morphogenetic protein-7 (3) and bone morphogenetic protein-14 (4). Daily cell counts were collected from phase contrast micrographs using the FIJI program. On the 4^th day, cells were fixed and stained with phalloidin for F-actin and DAPI for nuclear DNA, and imaged using a laser confocal microscope. The growth rate for cells in each condition were calculated by mathematically modeling the cells in their exponential growth phase. Growth rates of annulus fibrosus and nucleus pulposus cells were not significantly affected by the presence of bone morphogenetic proteins. The growth rate was the same for both cell types. Cells were spindle shaped with long protrusions and cell morphology did not appear qualitatively different between cell types. Bone morphogenetic proteins’ potential as regenerative therapies are supported by their influence of extracellular matrix synthesis rather than their stimulation of cell proliferation. The changes in intervertebral disc cells’ nutrient consumption under the influence of growth factors requires further investigation.