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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
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Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

Telomerase reverse transcriptase mediates bone formation for osteoporosis via activating BMP4/Smad1 pathway

Jinjin Ma1,2, Xiaonan Yuan1,2, Yao Xiao1

  • 1Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, Interdisciplinary Innovation Center for Nanomedicine, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, China.

Journal of Orthopaedic Translation
|May 11, 2026
PubMed
Abstract

Insights

Telomerase reverse transcriptase (TERT) regulates bone formation by activating the BMP4/Smad1 pathway. A novel aptamer-functionalized exosome therapy (Apt-TERT-Exo) shows promise for treating osteoporosis.

Area of Science:

  • Bone Biology and Metabolism
  • Regenerative Medicine
  • Biotechnology

Background:

  • The role of telomerase reverse transcriptase (TERT) in bone metabolism is not well understood.
  • Osteoporosis (OP) pathogenesis and potential therapeutic strategies involving TERT require further investigation.

Purpose of the Study:

  • To investigate the function of TERT in osteoporosis pathogenesis.
  • To explore the therapeutic potential of TERT-based interventions for osteoporosis.

Main Methods:

  • TERT expression analysis in clinical OP samples and ovariectomized (OVX) mouse models.
  • RNA sequencing, gain/loss-of-function studies, and pathway inhibition to elucidate mechanisms.
  • Development and evaluation of aptamer-functionalized TERT-overexpressing exosomes (Apt-TERT-Exo) in OVX mice.

Main Results:

  • TERT was found to be downregulated in osteoporosis, correlating with impaired osteogenesis.
  • TERT acts as a novel upstream activator of the pro-osteogenic BMP4/Smad1 pathway.
  • Apt-TERT-Exo demonstrated enhanced bone targeting and effectively restored bone mass in OVX mice by promoting osteogenesis.

Conclusions:

  • TERT is identified as a novel upstream regulator of osteogenesis through the BMP4/Smad1 pathway.
  • The Apt-TERT-Exo platform offers a promising targeted, cell-free therapeutic approach for osteoporosis treatment.
Keywords:
BMP4/Smad1 signalingBone-targeting aptamerDrug deliveryExosomeOsteoporosisTelomerase reverse transcriptase

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