The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin

Abstract

The antagonist-specific regulation in tissue engineering constitutes important attempts to achieve an improved and rapid bone regeneration by controlling the natural biological response of the natural body growth factors. L51P is molecularly engineered bone morphogentic protein-2 (BMP-2) variant with a substitution of the 51st leucine with a proline residue. L51P is deficient in BMP receptor binding, but maintains its structure and affinity for inhibitory proteins such as noggin, chordin, and gremlin. These modifications convert the BMP-2 variant L51P into a receptor-inactive inhibitor of BMP antagonists. This current approach may prevent the uncontrolled bone overgrowth using high concentration of BMPs and thus regulates the possible growth factor's high-dose side effects. Exploring of L51P biological functions is required to broad our understanding of BMP mutant biological functions and their potential clinical applications. The progress of L51P researches would hopefully lead to the development of multiple applications for using the L51P in bone and fracture healing disorders.

Exogenous Stimulation of Human Intervertebral Disc Cells in 3-Dimensional Alginate Bead Culture With BMP2 and L51P: Cytocompatibility and Effects on Cell Phenotype

“…Previous studies using L51P in combination with BMP2 have shown improved bone formation in a rat animal large bone defect model and rat calvaria cells. 16,[19][20][21] In these studies, no osteoinductive effect could be obtained with L51P application alone. Surprisingly, in our experiment, we observed a comparable effect of BMP2 and L51P single application in gene expression and GAG content.…”

“…Surprisingly, in our experiment, we observed a comparable effect of BMP2 and L51P single application in gene expression and GAG content. While the ligand-binding affinity of BMPRI to L51P is lower compared with BMP2, 16,17 the binding affinity of L51P to BMPRII is comparable to wild-type binding of BMP2. The binding affinity of L51P to BMP antagonists, such as NOG and GREM, was retained.…”

“…L51P has a lower affinity to BMPR type I (BMPRI) but binds to BMPR type II (BMPRII) with similar affinity as does wild-type BMP2. 16,17 The affinity for binding to the BMP antagonists, however, remains the same as for the wild-type. 16 Several studies have demonstrated the increased bioefficacy of exogenous and endogenous BMP2 if L51P was applied in combination in primary murine osteoblasts, MC3T3-E1, ATCDC5 and pro-myoblasts.…”

“…16,17 The affinity for binding to the BMP antagonists, however, remains the same as for the wild-type. 16 Several studies have demonstrated the increased bioefficacy of exogenous and endogenous BMP2 if L51P was applied in combination in primary murine osteoblasts, MC3T3-E1, ATCDC5 and pro-myoblasts. [18][19][20] Hauser et al 21 have even demonstrated improved bone formation by L51P and BMP2 in an in vivo mouse model.…”

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

“…The changes of indexes mentioned above were observed when Noggin, a BMP antagonist [29], was added to MC3T3-E1 cells. It showed that Noggin blocked MC3T3-E1 cells proliferation and ALP activity induced by icariin.…”