Low magnitude high frequency vibration promotes adipogenic differentiation of bone marrow stem cells via P38 MAPK signal

Abstract

Low magnitude high frequency vibration (LMHFV) has been mainly reported for its influence on the musculoskeletal system, particularly the bone tissue. In the bone structure, osteogenic activity is the main focus of study with regards to LMHFV. However, adipogenesis, another important mode of differentiation in the bone marrow cavity that might be affected by LMHFV, is much less researched. Furthermore, the molecular mechanism of how LMHFV influences adipogenesis still needs to be understood. Here, we tested the effect of LMHFV (0.3g, 40 Hz, amplitude: 50μm), 15min/d, on multipotent stem cells (MSCs), which are the common progenitors of osteogenic, chondrogenic, adipogenic and myogenic cells. It is previously shown that LMHFV promotes osteogenesis of MSCs. In this study, we further revealed its effect on adipo-differentiation of bone marrow stem cells (BMSCs) and studied the underlying signaling pathway. We found that when treated with LMHFV, the cells showed a higher expression of PPARγ, C/EBPα, adiponectin and showed more oil droplets. After vibration, the protein expression of PPARγ increased, and the phosphorylation of p38 MAPK was enhanced. After treating cells with SB203580, a specific p38 inhibitor, both the protein level of PPARγ illustrated by immunofluorescent staining and the oil droplets number, were decreased. Altogether, this indicates that p38 MAPK is activated during adipogenesis of BMSCs, and this is promoted by LMHFV. Our results demonstrating that specific parameters of LMHFV promotes adipogenesis of MSCs and enhances osteogenesis, highlights an unbeneficial side effect of vibration therapy used for preventing obesity and osteoporosis.

Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment

“…While most studies show proosteoblastic and antiadipocytic differentiation effects on MSCs [ 96 , 97 ], some contrary findings are reported. You’s group and Yu’s group found that LMHF vibration inhibited osteoblastic differentiation but promoted adipogenic differentiation of rat BM-MSCs [ 98 , 99 ]. You’s group reported that LMHF (0.3 g, 60 Hz, 1 h/1 day) vibration decreased osterix expression and inhibited mineralization in MSCs [ 98 ], while Yu’s group found that LMHF (0.3 g, 40 Hz, 15 min/day) vibration significantly increased the expression of PPARγ, C/EBPα , adiponectin , and the oil droplets [ 99 ].…”

“…You’s group and Yu’s group found that LMHF vibration inhibited osteoblastic differentiation but promoted adipogenic differentiation of rat BM-MSCs [ 98 , 99 ]. You’s group reported that LMHF (0.3 g, 60 Hz, 1 h/1 day) vibration decreased osterix expression and inhibited mineralization in MSCs [ 98 ], while Yu’s group found that LMHF (0.3 g, 40 Hz, 15 min/day) vibration significantly increased the expression of PPARγ, C/EBPα , adiponectin , and the oil droplets [ 99 ]. Yu’s study also demonstrated that LMHF vibration promoted adipogenic differentiation of MSCs through activating p38 MAPK signaling.…”

Vibration acceleration promotes endochondral formation during fracture healing through cellular chondrogenic differentiation

“…Additionally, LIPUS directly acts on mesenchymal stem cells, osteoblasts, chondrocytes, or osteoclasts and affects their proliferation or differentiation [17]. In several studies published recently, vibration acceleration has been reported to promote osteogenic or adipogenic differentiation from bone marrow stromal cells [47][48][49]. Furthermore, Marycz et al reported that vibration acceleration under the conditions of 0.3 G, 35 Hz, for 15 minutes per day enhanced the chondrogenic differentiation of human adipose-derived mesenchymal stromal stem cells [50].…”

Mechanical impact stimulation platform tailored for high-resolution light microscopy

“…The mechanical HF vibration has been applied to cell cultures with the aim to mimic the mechanical environment of cells in vivo [9][10][11][12][13][14][15][16]. The mechanical impact effects on cells, to our best knowledge, have not yet been tested, despite that they could potentially be more in vivo like for many cell types.…”

“…In the stimulation the cell culture is often moved either in parallel (i.e. vertical HF vibration) [9,11,[13][14][15]17] or perpendicularly (i.e. horizontal HF vibration) [10,12,18] to the direction of gravity.…”