HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles

Although various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-06, Vol.8 (1), p.9601-9601, Article 9601
Main Authors: Lee, Deokcheol, Taniguchi, Noboru, Sato, Katsuaki, Choijookhuu, Narantsog, Hishikawa, Yoshitaka, Kataoka, Hiroaki, Morinaga, Hidetaka, Lotz, Martin, Chosa, Etsuo
Format: Article
Language:English
Subjects:
Adipocytes
Adipogenesis
Adipose Tissue - cytology
Adipose Tissue - metabolism
Animals
Cartilage (articular)
Cell Differentiation
Degeneration
Gene Expression Regulation
HMGB2 Protein - genetics
HMGB2 Protein - metabolism
Male
Mesenchymal Stem Cells - cytology
Mesenchyme
Mice
Muscle, Skeletal - cytology
Platelet-derived growth factor
Rats
Receptors, Platelet-Derived Growth Factor - metabolism
Rotator cuff
Skeletal muscle
Stem cell transplantation
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2), which is a nuclear protein commonly associated with mesenchymal differentiation, is involved in the early articular cartilage degeneration. In this study, we addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co-localized with platelet-derived growth factor receptor α (PDGFRA) known as an MSC-specific marker, while their expressions were decreased during adipocytic differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis-related molecules were reduced, and adipogenic differentiation is substantially impaired in MSCs. Moreover, HMGB2 cells were generated in the muscle belly of rat supraspinatus muscles after rotator cuff transection, and some of these cells expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-28023-7