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.
Highlights
Low back pain, a considerable problem in today’s society [1], is associated with degeneration of the intervertebral disc (IVD) [2,3]
The cells cultured in the presence of BMP4 produced the highest amounts of GAGs, significant compared to BMP2 and BMP6 (p ≤ 0.001), but not BMP7
We have shown that bone morphogenetic proteins (BMPs), heterodimers, and their homodimer combinations induced proteoglycan formation and deposition, and deposition of type I and type II collagen by degenerated human nucleus pulposus (NP) cells
Summary
A considerable problem in today’s society [1], is associated with degeneration of the intervertebral disc (IVD) [2,3]. Growth factors are likely candidates to achieve biologic repair [5] Among these growth factors are the bone morphogenetic proteins (BMPs) from the transforming growth factor-β (TGF-β) superfamily, which are commonly known for their involvement in bone formation. Since their discovery in the 1960s, they have been found to play important roles throughout the entire body, including formation and maintenance of cartilaginous tissues [6]. BMP2 stimulates growth plate chondrocyte proliferation and hypertrophy to accelerate longitudinal bone growth [7], but was shown to be important in postnatal cartilage development and maintenance [8]
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