Inhibition of MSTN signal pathway may participate in LIPUS preventing bone loss in ovariectomized rats

J Bone Miner Metab. 2020 Jan;38(1):14-26. doi: 10.1007/s00774-019-01029-5. Epub 2019 Aug 14.

Abstract

Introduction: Menopause can lead to osteoporosis, which is characterized by destruction of bone microstructure, poor mechanical properties, and prone to fracture. LIPUS can effectively promote bone formation and fracture healing. MSTN is a transforming growth factor-β family member that acts as a negative regulator of skeletal muscle growth. A MSTN deficiency also has a positive effect on bone formation. However, whether LIPUS could inhibit bone loss and promote healing of bone injury of menopause through the inhibition of the MSTN signaling pathway has not been previously investigated. We herein investigated the effects of LIPUS on bone architecture, mechanical properties, the healing of bone defects, and its potential molecular mechanisms in ovariectomized rats.

Materials and methods: The rats were randomly divided into three groups: sham ovariectomized group (Sham), ovariectomized model group (OVX), ovariectomized model with LIPUS therapy group (OVX + LIPUS). The OVX + LIPUS rats were treated with LIPUS (1.5 MHz, 30 mW/cm2) on the femur for 20 min/day that lasted for 19 days.

Results: LIPUS effectively improved the bone microstructure, increased mechanical properties and promoted the healing of bone defects in ovariectomized rats. Moreover, LIPUS effectively decreased the MSTN content in serum and quadriceps muscle in ovariectomized rats, and inhibited the expression of MSTN downstream signaling molecules and activated the Wnt signaling pathway in the femur.

Conclusions: The present study shows that LIPUS improved osteoporosis and promoted bone defect healing in the ovariectomized rats may through the inhibition of the MSTN signal pathway.

Keywords: Bone defect healing; Bone microstructure; Low-intensity pulsed ultrasound; Myostatin; Osteoporosis.

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Biomechanical Phenomena
  • Body Weight
  • Bone Resorption / blood
  • Bone Resorption / prevention & control*
  • Female
  • Femur / diagnostic imaging
  • Femur / physiology
  • Gene Expression Regulation
  • Muscle Fibers, Skeletal / pathology
  • Muscles / pathology
  • Myostatin / metabolism*
  • Organ Size
  • Ovariectomy*
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Tartrate-Resistant Acid Phosphatase / blood
  • Ultrasonic Waves*
  • Uterus / pathology
  • Wnt Signaling Pathway

Substances

  • Myostatin
  • Alkaline Phosphatase
  • Tartrate-Resistant Acid Phosphatase