Osteoporosis Treatment: Targeting Osteoclast and Osteoblast Function with microRNA Therapeutics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 378

Special Issue Editor


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Guest Editor
Department of Medicine, Division of Rheumatology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA
Interests: bone; bone remodeling; skeletal pathogenesis; osteoporosis; osteoarthritis; inflammatory arthritis; heterotopic ossification; osteoclasts, osteoblasts; osteocytes; chondrocytes; mesenchymal stem cells (MSCs); microRNA; bone-homing recombinant adeno-associated virus (rAAV); cartilage-homing AAVs; ER stress

Special Issue Information

Dear Colleagues,

Osteoporosis is a common age-related disorder characterized by decreased bone mass and structural deterioration, leading to a heightened risk of fractures. It affects approximately 10 million individuals in the United States over the age of 50, with 1.5 million osteoporosis-related fractures occurring annually. This condition arises from an imbalance between bone formation by osteoblasts (OBs) and bone resorption by osteoclasts (OCs), with a shift favoring OC-mediated resorption. The current treatment options, including bisphosphonates and anti-RANK antibodies, target OCs in order to inhibit bone resorption but are limited by side effects and their inability to fully reverse the disease. Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) therapies, which enhance OB function, have shown efficacy but are hindered by high costs, frequent injection requirements, and a potential risk for osteosarcoma. Anti-sclerostin (SOST) antibodies promote OB differentiation but are also associated with adverse side effects and diminishing effectiveness over time. Thus, there is still a critical need for safe, effective, and durable therapies for osteoporosis. MicroRNAs (miRNAs) represent a promising class of disease-modifying agents for osteoporosis therapy. These small, highly conserved non-coding RNAs, approximately 22 nucleotides in length, regulate gene expression by binding to the 3′ untranslated region (3′-UTR) of target mRNAs, resulting in either mRNA degradation or translational inhibition. A growing body of evidence suggests that various miRNAs play crucial roles in bone biology by modulating the differentiation and activity of OBs and OCs. However, despite their potential as therapeutic agents, the clinical application of miRNAs must overcome several challenges, including efficient bone-targeted delivery and the achievement of long-term expression. Addressing these obstacles will be essential in developing miRNAs as viable therapeutic agents for osteoporosis.

Dr. Aijaz Ahmad John Bhat
Guest Editor

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Keywords

  • osteoporosis
  • microRNA
  • osteoblasts
  • osteoclasts
  • osteocytes
  • fracture
  • bone remodeling

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Published Papers (1 paper)

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Review

40 pages, 847 KB  
Review
The Growing Significance of microRNAs in Osteoporosis
by Alika Sarkar, Sana Sarkar, Afreen Anwar, Ji Woong Kim, Jae-Hyuck Shim and Aijaz Ahmad John
Cells 2025, 14(23), 1905; https://doi.org/10.3390/cells14231905 (registering DOI) - 1 Dec 2025
Abstract
Osteoporosis is an aging-related disease characterized by low bone mineral density and deteriorated bone structure, resulting in an increased risk of fractures. Currently, most osteoporosis therapies target osteoclasts to inhibit bone resorption, while the three FDA-approved anabolic agents include parathyroid hormone, parathyroid hormone-related [...] Read more.
Osteoporosis is an aging-related disease characterized by low bone mineral density and deteriorated bone structure, resulting in an increased risk of fractures. Currently, most osteoporosis therapies target osteoclasts to inhibit bone resorption, while the three FDA-approved anabolic agents include parathyroid hormone, parathyroid hormone-related protein, and anti-sclerostin antibody that promote osteoblast function. However, long-term treatment with these agents is associated with potential adverse effects and decreased therapeutic efficacy. This has prompted exploration of novel therapeutic strategies, including microRNAs (miRNAs), which are emerging as promising candidates. miRNAs have been reported to play important roles in regulating pathways involved in bone formation and resorption. In addition to their direct roles in osteoblasts and osteoclasts, miRNAs also serve as key mediators of communication between these cells, which is essential for maintaining bone homeostasis. The complexity of osteoporosis requires versatile regulators such as miRNAs that can modulate multiple biological pathways. Recent studies have demonstrated the potential of miRNA-based therapy to restore bone homeostasis in osteoporotic models. However, further studies are needed to develop tissue-specific delivery systems and evaluate long-term safety to improve the therapeutic potential of miRNAs as new osteoporosis drugs. Full article
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