Applying vibration in early postmenopausal osteoporosis promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells and suppresses postmenopausal osteoporosis progression

Abstract

We aimed to evaluate whether applying low magnitude vibration (LMV) in early postmenopausal osteoporosis (PMO) suppresses its progression, and to investigate underlying mechanisms. Rats were randomly divided into Sham (Sham-operated), Sham+V, OVX (ovariectomized), OVX+E2 (estradiol benzoate), OVX+V (LMV at 12–20 weeks postoperatively), and OVX+Vi (LMV at 1–20 weeks postoperatively) groups. LMV was applied for 20 min once daily for 5 days weekly. V rats were loaded with LMV at 12–20 weeks postoperatively. Vi rats were loaded with LMV at 1–20 weeks postoperatively. Estradiol (E2) rats were intramuscularly injected at 12–20 weeks postoperatively once daily for 3 days. The bone mineral densities (BMDs), biomechanical properties, and histomorphological parameters of tibiae were analyzed. In vitro, rat bone marrow-derived mesenchymal stem cells (rBMSCs) were subjected to LMV for 30 min daily for 5 days, or 17β-E2 with or without 1-day pretreatment of estrogen receptor (ER) inhibitor ICI 182,780 (ICI). The mRNA and protein expresion were performed. Data showed that LMV increased BMD, bone strength, and bone mass of rats, and the effects of Vi were stronger than those of E2. In vitro, LMV up-regulated the mRNA and protein expressions of Runx2, Osx, Col I, and OCN and down-regulated PPARγ, compared with E2. The effects of both LMV and E2 on rBMSCs were inhibited by ICI. Altogether, LMV in early PMO suppresses its progression, which is associated with osteogenic differentiation of rBMSCs via up-regulation of ERα and activation of the canonical Wnt pathway. LMV may therefore be superior to E2 for the suppression of PMO progression.

Low‐magnitude vibration induces osteogenic differentiation of bone marrow mesenchymal stem cells via miR‐378a‐3p/Grb2 pathway to promote bone formation in a rat model of age‐related bone loss

“…Three-point bending test would distinguish the differences in the mechanical properties of bone, as shown in previous 12,26,39,40 and our present studies. It is known that the mechanical testing of bone is a destructive process.…”

“…The three-point bending testing process has been described in our previous study. 12 Briefly, for the mechanical testing of the metaphysis, the proximal and distal ends of the left tibia were placed on supports with a span of approximately 40 mm, and an indenter was moved above the tibia at the point of 5 mm away from the proximal end of the tibial metaphysis and pressed down with a continuous displacement of 1 mm/min until the tibial metaphysis was broken. For the mechanical testing of the diaphysis, the damaged part of the tibial metaphysis was removed, and the remaining part of the tibia was placed on two supports with a span of 20 mm.…”

“…8,14,15 Our previous study showed that the application of LMV (vibrated at 0.9 g and 45 Hz, 30 min/day for 5 days) can promote the osteogenic differentiation of BMSCs to induce bone formation in postmenopausal osteoporosis rats. 12 Therefore, in the above safe and effective ranges of acceleration and frequency, six conditions (1, 0.3 g and 45 Hz; 2, 0.3 g and 90 Hz; 3, 0.5 g and 45 Hz; 4, 0.5 g and 90 Hz; 5, 0.9 g and 45 Hz; 6, 0.9 g and 90 Hz) were applied to aged rat-derived BMSCs to screen the optimal vibration condition. Each vibration group was vibrated for 30 minutes, once daily, after 5 days, the cells were used to analyze the expression levels of osteogenic genes.…”

“…In recent years, low‐magnitude vibration (LMV) that is a whole‐body vibration with acceleration less than 1 g (g = 9.81 m/s 2 ) has been concerned as a non‐pharmacologic approach for the prevention and treatment of osteoporosis due to its small side effects, simple operation, low cost, and relative safety 12 . Studies have shown that the vibration at the acceleration below 1 g is relatively safe, 13 and other studies have shown that the frequency of LMV between 20 and 90 Hz can effectively enhance the osteogenic differentiation of BMSCs 8,14,15 .…”

Low magnitude vibration alleviates age-related bone loss by inhibiting cell senescence of osteogenic cells in naturally senescent rats

“…As a non-drug, non-invasive systemic exercise therapy, low magnitude vibration (LMV) with acceleration less than 1 g (g = 9.81 m/s 2 ) had been proved to promote bone formation [ 13 ]. Studies had also reported that vibration with the acceleration <1 g and frequency 20-90 Hz can increase bone volume and bone density of humans and animal models [ 14 – 16 ].…”