Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Abstract

Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.

Polyetheretherketone and Its Composites for Bone Replacement and Regeneration

“…Rough Ti-PEEK disks induce the adhesion and proliferation of osteoblasts and upregulate the gene expressions including alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP-2) [116]. ALP activity is considered as an early marker of cell differentiation; BMP-2is the growth factor that promotes osteoblastic cell differentiation [117,118]. From the literature, human osteoblast-like osteosarcoma cells (MG63) cultured on the surfaces with increasing roughness show decreased proliferation and increased cell differentiation [119].…”

Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats

“…As regards delivery of BMPs through an open approach to an otherwise intact IVD (NP not intentionally removed), only one group has reported bone formation with BMP7 delivery, despite their intention to drive canine IVD regeneration 52 . All other studies reviewed that delivered factors or gene-therapy through open approaches to intact IVDs to date have shown the NP cells to be reactive to BMPs in such a way to drive glycosaminoglycan and proteoglycan production, restore IVD height and MRI hydration signal in damaged IVDs, and to not induce bone production within the IVD 53 – 58 . Most of the BMP delivery to IVDs has been of homodimeric forms of BMP2, BMP7 and BMP-14, but more recent reports using the hyper-osteoinductive 59 – 61 heterodimer BMPs, have also demonstrated disc regenerative and protective effects and not fusions or bone induction in vitro 58 and in vivo 62 , or absent in vivo disc/bone anabolic effects 63 .…”

“…All other studies reviewed that delivered factors or gene-therapy through open approaches to intact IVDs to date have shown the NP cells to be reactive to BMPs in such a way to drive glycosaminoglycan and proteoglycan production, restore IVD height and MRI hydration signal in damaged IVDs, and to not induce bone production within the IVD 53 – 58 . Most of the BMP delivery to IVDs has been of homodimeric forms of BMP2, BMP7 and BMP-14, but more recent reports using the hyper-osteoinductive 59 – 61 heterodimer BMPs, have also demonstrated disc regenerative and protective effects and not fusions or bone induction in vitro 58 and in vivo 62 , or absent in vivo disc/bone anabolic effects 63 . BMP heterodimers strongly increase fusion in animal posterolateral fusion models 59 , 64 , 65 , but their effectiveness has not been reported for comparative anterior IVD fusions.…”

Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

“…Previously, we compared BMP-2, BMP-4, BMP-6, BMP-7, and their combinations and heterodimers, for their regenerative effect on the pellet culture model of human NP cells or NP cells co-cultured with bone marrow mesenchymal stromal cells [ 23 ]. In this study, BMP-4 was identified as the most potent in inducing glycosaminoglycan production and deposition, suggesting a regenerative effect could be achieved upon direct intradiscal injection [ 23 ]. In order to investigate the applicability of BMP-4 for IVDD treatment, the effects of BMP-4 on IVDD were evaluated in the present study in vitro and in a large animal model of IVDD.…”