Title:Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Disc and Mesenchymal Stromal Cells
Volume: 14
Issue: 8
Author(s): Rahel Deborah May, Daniela Angelika Frauchiger, Christoph Emmanuel Albers, Adel Tekari, Lorin Michael Benneker, Frank Michael Klenke, Willy Hofstetter and Benjamin Gantenbein*
Affiliation:
- Department for BioMedical Research (DBMR), University of Bern, Bern,Switzerland
Keywords:
Spinal fusion, intervertebral discs, mesenchymal stromal cells, osteogenesis, bone morphogenetic proteins, antagonists
of bone morphogenetic proteins.
Abstract: Low back pain is a prevalent socio-economic burden and is often associated with damaged
or degenerated intervertebral discs (IVDs). When conservative therapy fails, removal of the IVD (discectomy),
followed by intersomatic spinal fusion, is currently the standard practice in clinics. The
remaining space is filled with an intersomatic device (cage) and with bone substitutes to achieve disc
height compensation and bone fusion. As a complication, in up to 30% of cases, spinal non-fusions
result in a painful pseudoarthrosis. Bone morphogenetic proteins (BMPs) have been clinically applied
with varied outcomes. Several members of the BMP family, such as BMP2, BMP4, BMP6, BMP7,
and BMP9, are known to induce osteogenesis. Questions remain on why hyper-physiological doses of
BMPs do not show beneficial effects in certain patients. In this respect, BMP antagonists secreted by
mesenchymal cells, which might interfere with or block the action of BMPs, have drawn research
attention as possible targets for the enhancement of spinal fusion or the prevention of non-unions.
Examples of these antagonists are noggin, gremlin1 and 2, chordin, follistatin, BMP3, and twisted
gastrulation. In this review, we discuss current evidence of the osteogenic effects of several members
of the BMP family on osteoblasts, IVD cells, and mesenchymal stromal cells. We consider in vitro and
in vivo studies performed in human, mouse, rat, and rabbit related to BMP and BMP antagonists in the
last two decades. We give insights into the effects that BMP have on the ossification of the spine. Furthermore,
the benefits, pitfalls, and possible safety concerns using these cytokines for the improvement
of spinal fusion are discussed.
