Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Discs, and Mesenchymal Stromal Cells.

May, Rahel Deborah; Frauchiger, Daniela Angelika; Albers, Christoph Emmanuel; Tekari, Adel; Benneker, Lorin Michael; Klenke, Frank Michael; Hofstetter, Wilhelm; Gantenbein, Benjamin (2019). Application of Cytokines of the Bone Morphogenetic Protein (BMP) Family in Spinal Fusion - Effects on the Bone, Intervertebral Discs, and Mesenchymal Stromal Cells. Current stem cell research & therapy, 14(8), pp. 618-643. Bentham Science Publishers 10.2174/1574888X14666190628103528

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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 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.

Item Type:	Journal Article (Review Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung 04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
UniBE Contributor:	Albers, Christoph E., Benneker, Lorin Michael, Klenke, Frank M., Hofstetter, Wilhelm (B), Gantenbein, Benjamin
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1574-888X
Publisher:	Bentham Science Publishers
Language:	English
Submitter:	Kathrin Aeschlimann
Date Deposited:	28 Oct 2019 08:56
Last Modified:	02 Mar 2023 23:32
Publisher DOI:	10.2174/1574888X14666190628103528
PubMed ID:	31455201
Uncontrolled Keywords:	Spinal fusion antagonists of bone morphogenetic proteinSpinal fusion antagonists of bone morphogenetic proteins bone morphogenetic proteins intervertebral discs mesenchymal stromal cells osteogenesis
URI:	https://boris.unibe.ch/id/eprint/134161