MSTN is a key mediator for low-intensity pulsed ultrasound preventing bone loss in hindlimb-suspended rats

Tang, Liang; An, Shasha; Zhang, Zhihao; Fan, Xiushan; Guo, Jianzhong; Sun, Lijun; Ta, Dean

Affiliations

¹Institute of Sports Biology, Shaanxi Normal University, Xi'an 710119, China

²Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University, Xi'an 710119, China

³Department of Electronic Engineering, Fudan University, Shanghai 200433, China

⁴Human Phenome Institute, Fudan University, Shanghai 201203, China

⁵ Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention (MICCAI) of Shanghai, Shanghai 200032, China

Abstract and keywords

Low-intensity pulsed ultrasound (LIPUS) has been used to accelerate bone fracture healing. However, the issue whether LIPUS is effective in preventing osteoporosis has not been clarified, and if so, what possible mechanisms might be responsible. Myostatin (MSTN) is a negative regulator of muscle growth, and its absence will trigger a positive response to bone. In this study, we examined the effects of LIPUS on bone micro-structure, mechanical properties and damage healing of hindlimb-suspended rats, and investigated whether the inhibition of MSTN plays a role in this process. The rats were randomly divided into four groups: Normal control group (NC), Hind limb suspension group (HLS), Hind limb suspension and 80 mW/cm² LIPUS irradiation group (HLS+ 80 mW/cm²), Hind limb suspension and 30 mW/cm² LIPUS irradiation group (HLS+ 30 mW/cm²). The HLS+ 80 mW/cm² rats were treated with LIPUS (1 MHz, 80 mW/cm²) and the HLS+ 30 mW/cm² rats were treated with LIPUS (1 MHz, 30 mW/cm²) on the femur for 20 min/day for 28 days. MC3T3-E1 cells were respectively cultured with the serum of wild type mouse and MSTN knockout mouse at 1% concentration for 7 days. After 28 days, LIPUS effectively prevented the destruction of bone microstructure and the decline of mechanical properties, and promoted bone defect healing in the tail-suspended rats. In addition, LIPUS effectively reduced the MSTN content in the quadriceps and serum of the tail-suspended rats, inhibited its receptor and downstream signaling molecules and activated the Wnt signaling pathway in femurs. Growth of MC-3T3-E1 cell cultured with the serum of MSTN knockout mice was superior to that with wild mice serum on day 7. These results indicate that MSTN is a key mediator in LIPUS preventing bone loss caused by hindlimb-suspension.

Keywords: Disuse osteopenia; Osteoporosis; Low intensity pulsed ultrasound; Myostatin; Hind limb suspension

Links

DOI: 10.1016/j.bone.2020.115610

PubMed: 32829040

WoS: 000604733200008

History

Received: 2019-12-11

Revised: 2020-08-18

Accepted: 2020-08-18

Online: 2020-08-21

Cited Works (8)

Year	Entry
2019	Bullock WA, Hoggatt AM, Horan DJ, Lewis KJ, Yokota H, Hann S, Warman ML, Sebastian A, Loots GG, Pavalko FM, Robling AG. Expression of a degradation‐resistant β‐catenin mutant in osteocytes protects the skeleton from mechanodeprivation‐induced bone wasting. J Bone Miner Res. October 2019;34(10):1964-1975.
2000	LeBlanc A, Schneider V, Shackelford L, West S, Oganov V, Bakulin A, Voronin L. Bone mineral and lean tissue loss after long duration space flight. J Musculoskel Neuron Interact. 2000;1(2):157-160.
1998	Zerwekh JE, Ruml LA, Gottschalk F, Pak CYC. The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res. October 1998;13(10):1594-1601.
2002	Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. June 1, 2002;359(9321):1929-1936.
2004	Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long‐duration spaceflight. J Bone Miner Res. June 2004;19(6):1006-1012.
2006	Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. May 2006;116(5):1202-1209.
2002	Burr DB, Robling AG, Turner CH. Effects of biomechanical stress on bones in animals. Bone. May 2002;30(5):781-786.
2014	Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. October 2014;25(10):2359-2381.