Scholarlink

Background <p>Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use is often associated with adverse effects, highlighting the need for safer, more sustainable therapeutic strategies. This study investigates the pro-osteogenic and anti-resorptive potential of the secretome from <i>Smurf1</i>-silenced mesenchymal stem cells (MSCs) as a promising cell-free therapy for bone regeneration.</p> Methods <p>Conditioned media (CM) from <i>Smurf1</i>-silenced rat (rCM-<i>Smur1</i>) and human MSCs (hCM-<i>Smurf1</i>) was collected and analyzed. Pro-osteogenic potential was assessed by measuring in vitro mineralization in human and rat MSCs cultures. In vivo, studies were conducted using a rat ectopic bone formation model and a post-menopausal osteoporotic mouse model. Additionally, primary human osteoporotic MSCs were preconditioned with hCM-<i>Smurf1</i>, and their osteogenic capacity was compared to that induced by BMP2 treatment. Ex vivo, human bone explants were treated with hCM-<i>Smurf1</i> to assess anti-resorptive effects. Proteomic analysis of the soluble and vesicular CM fractions identified key proteins involved in bone regeneration.</p> Results <p>CM from <i>Smurf1</i>-silenced MSCs significantly enhanced mineralization in vitro and bone formation in vivo. Preconditioning human osteoporotic MSCs with hCM-<i>Smurf1</i> significantly increases in vitro mineralization, with levels comparable to those achieved with BMP2 treatment. Additionally, in ex vivo human bone cultures, treatment with hCM-<i>Smurf1</i> significantly reduced RANKL expression without affecting OPG levels, indicating an anti-resorptive effect. In vivo, CM from <i>Smurf1</i>-silenced MSCs significantly increased bone formation in a rat ectopic model, and its local administration reduced trabecular bone loss by 50% in a post-menopausal osteoporotic mouse model after a single administration within just four weeks<i>.</i> Proteomic analysis revealed both soluble and vesicular fractions of hCM-<i>Smurf1</i> were enriched with proteins essential for ossification and extracellular matrix organization, enhancing osteogenic differentiation.</p> Conclusions <p>The <i>Smurf1</i>-silenced MSCs' secretome shows potent osteogenic and anti-resorptive effects, significantly enhancing bone formation and reducing bone loss. This study provides compelling evidence for the therapeutic potential of <i>Smurf1</i>-silenced MSC-derived secretome as a non-toxic and targeted treatment for osteoporosis. These findings warrant further in vivo studies and clinical trials to validate its therapeutic efficacy and safety.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Paracrine activity of Smurf1-silenced mesenchymal stem cells enhances bone regeneration and reduces bone loss in postmenopausal osteoporosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月7日

查看全文
  • Alberto González-González,
  • Itziar Álvarez-Iglesias,
  • Daniel García-Sánchez,
  • Monica Dotta,
  • Ricardo Reyes,
  • Ana Alfonso-Fernández,
  • Alfonso Bolado-Carrancio,
  • Patricia Díaz-Rodríguez,
  • María Isabel Pérez-Núñez,
  • José Carlos Rodríguez-Rey,
  • Jesús Delgado-Calle,
  • Flor M. Pérez-Campo

摘要

Background

Osteoporosis (OP), characterized by reduced bone mass and mineral density, is a global metabolic disorder that severely impacts the quality of life in affected individuals. Although current pharmacological treatments are effective, their long-term use is often associated with adverse effects, highlighting the need for safer, more sustainable therapeutic strategies. This study investigates the pro-osteogenic and anti-resorptive potential of the secretome from Smurf1-silenced mesenchymal stem cells (MSCs) as a promising cell-free therapy for bone regeneration.

Methods

Conditioned media (CM) from Smurf1-silenced rat (rCM-Smur1) and human MSCs (hCM-Smurf1) was collected and analyzed. Pro-osteogenic potential was assessed by measuring in vitro mineralization in human and rat MSCs cultures. In vivo, studies were conducted using a rat ectopic bone formation model and a post-menopausal osteoporotic mouse model. Additionally, primary human osteoporotic MSCs were preconditioned with hCM-Smurf1, and their osteogenic capacity was compared to that induced by BMP2 treatment. Ex vivo, human bone explants were treated with hCM-Smurf1 to assess anti-resorptive effects. Proteomic analysis of the soluble and vesicular CM fractions identified key proteins involved in bone regeneration.

Results

CM from Smurf1-silenced MSCs significantly enhanced mineralization in vitro and bone formation in vivo. Preconditioning human osteoporotic MSCs with hCM-Smurf1 significantly increases in vitro mineralization, with levels comparable to those achieved with BMP2 treatment. Additionally, in ex vivo human bone cultures, treatment with hCM-Smurf1 significantly reduced RANKL expression without affecting OPG levels, indicating an anti-resorptive effect. In vivo, CM from Smurf1-silenced MSCs significantly increased bone formation in a rat ectopic model, and its local administration reduced trabecular bone loss by 50% in a post-menopausal osteoporotic mouse model after a single administration within just four weeks. Proteomic analysis revealed both soluble and vesicular fractions of hCM-Smurf1 were enriched with proteins essential for ossification and extracellular matrix organization, enhancing osteogenic differentiation.

Conclusions

The Smurf1-silenced MSCs' secretome shows potent osteogenic and anti-resorptive effects, significantly enhancing bone formation and reducing bone loss. This study provides compelling evidence for the therapeutic potential of Smurf1-silenced MSC-derived secretome as a non-toxic and targeted treatment for osteoporosis. These findings warrant further in vivo studies and clinical trials to validate its therapeutic efficacy and safety.