Bone morphogenetic protein‐2 is a stronger inducer of osteogenesis within muscle tissue than heterodimeric bone morphogenetic protein‐2/6 and ‐2/7: Implications for expedited gene‐enhanced bone repair

Betz, Volker M.; Ren, Bin; Messmer, Carolin; Jansson, Volkmar; Betz, Oliver B.; Müller, Peter E.

doi:10.1002/jgm.3042

Cited by 9 publications

(12 citation statements)

References 43 publications

(92 reference statements)

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“…Here, the high concentration of homodimeric BMP‐2 most effectively elicited osteogenesis within adipose tissue fragments, whereas its low concentration had a similar effect as the most potent heterodimer BMP‐2/7 at the high concentration. The results of the present experiment, in turn, are in agreement with a previous study of our group comparing the effects of BMP‐2, BMP‐2/6 and BMP‐2/7 on muscle tissue fragments in vitro 44 . In this experiment, BMP‐2 had a stronger effect on gene and protein expression of bone‐specific markers and calcium deposition within muscle tissue.…”

Section: Discussionsupporting

confidence: 93%

“…The results of the present experiment, in turn, are in agreement with a previous study of our group comparing the effects of BMP-2, BMP-2/6 and BMP-2/7 on muscle tissue fragments in vitro. 44 In this experiment, BMP-2 had a stronger effect on gene and protein expression of bone-specific markers and calcium deposition within muscle tissue. A recent study reports that the effect of BMP heterodimers depends on the cell type.…”

Section: Discussionmentioning

confidence: 70%

“…A recent study reports that the effect of BMP heterodimers depends on the cell type 45 . Heterodimeric BMPs may have a stronger osteogenic effect on preosteoblasts 45 than on cells residing within muscle tissue 44 and adipose‐derived cells 43 . This may be the reason why several in vivo bone healing studies revealed favorable effects of BMP heterodimers.…”

Section: Discussionmentioning

confidence: 99%

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Osteoinduction within adipose tissue fragments by heterodimeric bone morphogenetic Proteins‐2/6 and ‐2/7 versus homodimeric bone morphogenetic protein‐2: Therapeutic implications for bone regeneration

Betz¹,

Ren²,

Betz

et al. 2021

The Journal of Gene Medicine

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Background Fragments of subcutaneous adipose tissue that have been genetically modified to express bone morphogenetic protein‐2 (BMP‐2) regenerate large segmental osseous lesions in rodents. Gene‐activated adipose tissue can be implanted into osseous defects without prior cell extraction and cell culture. The present study aimed to explore whether the heterodimers BMP‐2/6 or BMP‐2/7 exceed the osteoinductive effect of BMP‐2 on adipose tissue. Methods In an in vitro tissue culture system, freshly harvested rat subcutaneous adipose tissue was cultivated in the presence of either BMP‐2 or BMP‐2/6 or BMP‐2/7 at a high (200 ng/ml) and low (50 ng/ml) concentration. Gene expression analysis as well as histological and immunohistochemical methods were applied to test for osteoinduction. Results A concentration of 200 ng/ml of homodimeric BMP‐2 induced osteogenic differentiation most potently, showing more calcification and a higher expression level of bone markers than both concentrations of BMP‐2/6 or ‐2/7. A concentration of 50 ng/ml of BMP‐2 was a significantly stronger osteogenic inducer than both concentrations of BMP‐2/6 and the low concentration of BMP‐2/7. The most potent heterodimeric driver of osteoinduction was BMP‐2/7 at a high concentration, demonstrating effects similar to those of BMP‐2 at a low concentration. Conclusions Homodimeric BMP‐2 evoked osteoinduction within adipose tissue more potently and at a lower concentration than heterodimeric BMP‐2/6 or BMP‐2/7. This result agrees well with the fact that it might be easier to translate adipose grafts activated by homodimeric BMP‐2 clinically. Preclinical in vivo gene transfer studies are necessary to confirm the results of the present study.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Osteoinduction within adipose tissue fragments by heterodimeric bone morphogenetic Proteins‐2/6 and ‐2/7 versus homodimeric bone morphogenetic protein‐2: Therapeutic implications for bone regeneration

Betz¹,

Ren²,

Betz

et al. 2021

The Journal of Gene Medicine

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“…Western blot can be used to detect the expression of bone morphogenetic protein 2 [ 19 ]. Bone morphogenetic protein 2 (BMP 2) is a bone formation promoter and a member of the transforming growth factor beta superfamily [ 20 ]. Bone morphogenetic protein 2 can promote the expression of osteocalcin and alkaline phosphatase and promote the synthesis of osteopontin, osteocalcin, and type I collagen and the mineralization of extracellular matrix [ 21 , 22 ], thereby promoting osteoblasts and the maturation, proliferation, and differentiation of osteoblasts and induces new bone formation in vivo and in vitro [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Coculture Fibroblasts and Vascular Endothelial Cells on Proliferation and Osteogenesis of Adipose Stem Cells

Liao

Zhong

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. The development of tissue engineering provides a new method for the clinical treatment of bone defects, but the problems of slow formation and slow vascularization of tissue engineered bone have always existed. Studies have shown that the combined culture system of vascular endothelial cells and adipose stem cells is superior to single cell in repairing bone defects. With the excellent proliferation ability, secretion of synthetic collagen and a variety of regulatory factors and fibroblasts can differentiate into osteoblasts and have the potential to be excellent seed cells involved in tissue engineering bone construction. Objective. To investigate the effects of combined culture of fibroblasts, vascular endothelial cells, and adipose stem cells on proliferation and osteogenic differentiation of adipose stem cells. Methods. The cells were divided into 4 groups: adipose stem cell group, adipose stem cell+vascular endothelial cell coculture group, adipose stem cell+fibroblast coculture group, and adipose stem cell+vascular endothelial cell+fibroblast coculture group. The morphological changes of the cells were observed under an inverted microscope. After 1, 3, 5, 7, and 9 days of coculture, the proliferation of adipose stem cells in each group was detected by a CCK-8 method and the growth curve was plotted. Adipose stem cells in each group were stained with alizarin red and alkaline phosphatase at days 7, 14, 21, and 28. At the third week of coculture, Western blot was used to detect the expression level of bone morphogenetic protein 2 of adipose stem cells in each group. Results and Conclusions. (1) After 14 days of culture, some cells in the adipose stem cell+vascular endothelial cell+fibroblast coculture group fused into clumps and distributed in nests, while the adipose stem cells in the adipose stem cell group had a single cell morphology and no cell clusters were observed. (2) The cell growth curves were basically the same in each group, and the absorbance value increased gradually. The absorbance value of the adipocyte+vascular endothelial cell+fibroblast coculture group was the highest, followed by the adipocyte+fibroblast coculture group and then the adipocyte+fibroblast coculture group. (3) Alizarin red staining showed negative reaction in each group on the 7th day, and a small number of red positive cells gradually appeared in each group as time went on. On the 28th day, red positive cells were found in all groups, and most of them were in the coculture group of adipose stem cells+vascular endothelial cells+fibroblasts, showing red focal. The coculture group of adipose stem cells+vascular endothelial cells and adipose stem cells+fibroblasts was less, and the adipose stem cell group was the least. On day 28 of alkaline phosphatase staining, cells in each group had red positive particles, and the adipose stem cell+vascular endothelial cell+fibroblast coculture group and adipose stem cell+fibroblast coculture group had the most, followed by the adipose stem cell+vascular endothelial cell coculture group and then the adipose stem cell group. (4) Bone morphogenetic protein 2 was expressed in all groups, especially in adipose stem cell+fibroblast coculture group and adipose stem cell+vascular endothelial cell+ fibroblast coculture group. (5) Fibroblast could promote adipose stem cell osteogenic differentiation better than vascular endothelial cells, but the proliferation effect was not as good as vascular endothelial cells. The coculture system of fibroblast combined with vascular endothelial cells and adipose stem cells promoted the proliferation of adipose stem cells and the rapid and efficient differentiation of adipose stem cells into osteoblasts.

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“…Retinal ganglion cells transplanted in the retina which is a modified form of stem cells and induced pluripotent stem to encourage their survival in the eye [30]. Mostly degeneration of photoreceptors occur due to the absence of retinal pigment epithelium leading to vision loss, integration of photoreceptors may improve visual function [31]. Mainstream of stem cell therapy concentrate on embryonic stem cells due to their strong pluripotency.…”

Section: Introductionmentioning

confidence: 99%

Restoring Vision by Regenerative Medicine Using Stem Cell: A Review

Rk¹,

Ibrahim²,

Shafiq³

et al. 2018

J Biomol Res Ther

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Restoring vision is the most important center of attention of our research program, On the other hand, to attain our objective and convey the preeminent eminence of stem cell therapy; we have to understand the fundamental biology of stem cells. (RPE) Retinal Pigmented epithelium layer degenerates and contributing to a succession of actions resulting in visual impairments. Regenerative medicine holds promise for the spanning almost for all body system and the eye is an ideal organ to use in research because it is the only part of nervous system that is the visible and easily accessible. This review outlines advances in therapy and the main spotlight for the improvement and advance of cell therapies that are being confronted today.

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Bone morphogenetic protein‐2 is a stronger inducer of osteogenesis within muscle tissue than heterodimeric bone morphogenetic protein‐2/6 and ‐2/7: Implications for expedited gene‐enhanced bone repair

Cited by 9 publications

References 43 publications

Osteoinduction within adipose tissue fragments by heterodimeric bone morphogenetic Proteins‐2/6 and ‐2/7 versus homodimeric bone morphogenetic protein‐2: Therapeutic implications for bone regeneration

Osteoinduction within adipose tissue fragments by heterodimeric bone morphogenetic Proteins‐2/6 and ‐2/7 versus homodimeric bone morphogenetic protein‐2: Therapeutic implications for bone regeneration

Effects of Coculture Fibroblasts and Vascular Endothelial Cells on Proliferation and Osteogenesis of Adipose Stem Cells

Restoring Vision by Regenerative Medicine Using Stem Cell: A Review

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