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.

Autor: Betz VM; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, LMU, Munich, Bavaria, Germany., Ren B; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, LMU, Munich, Bavaria, Germany., Betz OB; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, LMU, Munich, Bavaria, Germany.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Jansson V; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, LMU, Munich, Bavaria, Germany., Müller PE; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, LMU, Munich, Bavaria, Germany.
Jazyk: angličtina
Zdroj: The journal of gene medicine [J Gene Med] 2021 Mar; Vol. 23 (3), pp. e3311. Date of Electronic Publication: 2021 Feb 01.
DOI: 10.1002/jgm.3311
Abstrakt: 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.
(© 2021 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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