MiR-378: A Prognostic Marker and Therapeutic Target For Osteoporosis
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MiR-378: A Prognostic Marker and Therapeutic Target For Osteoporosis

23.09.2025 Compuscript Ltd
Osteoporosis is a degenerative disease characterized by decreased bone mass and damage to bone microarchitecture, as well as increased bone fragility. Previous research showed that the conserved microRNA-378 (miR-378) suppresses bone marrow stromal cell (BMSC) osteogenesis and hinders fracture healing, but its precise role in osteoporosis remains unclear.

This research, published in the Genes & Diseases journal by a team from Chinese Academy of Sciences and The Chinese University of Hong Kong, examined miR-378 in an ovariectomy (OVX)–induced osteoporosis model, exploring both osteoclastogenesis and osteogenesis.

Three-dimensional imaging and histological staining showed that miR-378–overexpressing transgenic (Tg) mice experienced significantly lower bone mineral density, thinner trabeculae, and reduced calcium deposition after OVX surgery. Additionally, miR-378 increased BMSC’s osteoclastogenesis by activating both the canonical and non-canonical nuclear factor kappa-light-chain-enhancer of activated B (NF- κB) signaling pathways.

In silico analysis results identified tumor necrosis factor receptor-associated factor 3 (Traf3) as one of the direct target genes for miR-378-5p and its knockdown may result in severe osteoclastogenesis. Further experiments indicated that miR-378 overexpression elevated transforming growth factor beta (TGFβ), which impaired BMSC osteogenesis by downregulating Wnt/β-catenin signaling in a Traf3-dependent manner.

Remarkably, intravenous injection of an anti-miR-378 lentiviral therapy via tail-vein injection reversed bone loss, restored bone formation rates, and reduced osteoclast numbers, significantly improving bone microarchitecture in OVX mice.

While these collective data highlight the key role of miR-378 in OVX-induced osteoporosis, additional studies are needed to confirm the efficacy of anti-miR-378 therapy in wild-type mice. In conclusion, targeting miR-378 could offer a dual-action strategy, simultaneously inhibiting bone resorption and boosting bone formation. This dual action positions miR-378 inhibitors as compelling candidates for next-generation osteoporosis therapies, especially for postmenopausal women.

Reference

Title of Original Paper: MiR-378 mediates the ovariectomy induced bone loss via exaggerating osteoclastogenesis and transforming growth factor beta impaired osteogenesis

Journal: Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2025.101754

Funding Information:
  • The National Natural Science Foundation of China (No. 82172430 and 82272505)
  • University Grants Committee, Research Grants Council of the Hong Kong Special Administrative Region, China (No. 14108720, 14121721, 14202920, N_CUHK472/22, C7030-18G, T13-402/17-N and AoE/M-402/20)
  • Health and Medical Research Fund (HMRF) Hong Kong, China (No. 16170951, 17180831, 08190416 and 09203436)
  • Hong Kong Innovation Technology Commission Funds, China (No. PRP/050/19FX)
  • The Health@InnoHK program launched by Innovation Technology Commission of the Hong Kong SAR, China

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus Cite Score: 8.4 | Impact Factor: 9.4

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https://tinyurl.com/549ynfn9
Lu Feng, Zhengmeng Yang, Nan Hou, Haixing Wang, Shanshan Bai, Xuan Lu, Yaofeng Wang, Sien Lin, Micky D. Tortorella, Gang Li,
MiR-378 mediates the ovariectomy induced bone loss via exaggerating osteoclastogenesis and transforming growth factor beta impaired osteogenesis,
Genes & Diseases,
2025,
101754,
ISSN 2352-3042,
https://doi.org/10.1016/j.gendis.2025.101754.
Angehängte Dokumente
  • A. Three-dimensional reconstruction of trabecular bone in the distal metaphysis of miR-378 TG mice after anti-NC and anti-miR-378 mediated lentivirus injection. Scale bar, 100 μM. B-D. Microstructure parameters including bone volume/tissue volume (BV/TV) (B), bone mineral density (BMD) (C) and trabecular thickness (Tb.Th) (D) of the trabecular bone in different groups. E. Representative images of Von Kossa staining, in vivo double labels and Toluidine blue staining of femoral metaphysis. White arrow indicates the bone distance between two labeling which reflects the mineral apposition rate. Red arrow indicates the osteoblasts. Scale bar: 400 μM for Von Kossa, 100 μM for in vivo labeling and Toluidine blue staining. F-H. Histomorphometric analysis of distal femur sections including N.Ob/BS (G), N.Oc/BS (H) and MAR (I) (n=8; *p<0.05, **p<0.01, ***p<0.001). I. TRAP staining and IHC staining of femoral metaphysis using Ocn and Traf3 antibodies. Red arrow indicates the TRAP positive cells. Scale bar: 200 μM
  • A. Three-dimensional reconstruction of trabecular bone in the distal metaphysis of WT and miR-378 TG mice after sham and OVX treatment. Scale bar, 100 μM. B-D. Microstructure parameters including bone volume/tissue volume (BV/TV) (B), bone mineral density (BMD) (C) and trabecular thickness (Tb.Th) (D) of the trabecular bone in different groups. E-I. Representative images of Von Kossa staining (E), in vivo double labels (F) and Toluidine blue staining (G) of femoral metaphysis as well as IHC staining using TRAP (H) and OCN (I) antibodies. White arrow indicates the bone distance between two labeling which reflects the mineral apposition rate. Red arrow indicates the osteoblasts. Green arrow indicated the TRAP positive cells. Scale bar: 400 μM for Von Kossa, 100 μM for in vivo labeling and Toluidine blue staining, 200 μM for IHC staining. J-L. Histomorphometric analysis of distal femur sections including N.Ob/BS (number of osteoblasts per bone surface) (J), N.Oc/BS (number of osteoclast per bone surface) (K) and MAR (mineral apposition rate) (L) (n=8; *p<0.05, **p<0.01, ***p<0.001).
  • A. ALP staining and Alizarin Red S staining of BMSCs from WT and miR-378 Tg mice upon sham and OVX operations, respectively and osteogenic induced for 7 days. Scale bar: 10 mm. B&C. Quantitative analysis of ALP activities (B) and ARS staining intensities (C). D-F. The mRNA expression level of osteogenesis markers including Runx2 (D), Ocn (E) and Opn (F) measured by real-time PCR. G-I. Total TNF〈 (G), IFN© (H) and TGFβ (I) serum levels in WT and miR-378 Tg mice after sham and OVX surgery. J. ALP staining and Alizarin Red S staining of BMSCs from WT and miR-378 Tg mice pretreated with TGFβ. Scale bar: 10 mm. K&L. Quantitative analysis of ALP activities (K) and ARS staining intensities (L). M-O. The mRNA expression level of osteogenesis markers including Runx2 (M), Ocn (N) and Opn (O) measured by real-time PCR (n=6; *p<0.05, **p<0.01, ***p<0.001).
23.09.2025 Compuscript Ltd
Regions: Europe, Ireland, Asia, China, Hong Kong
Keywords: Science, Life Sciences, Health, Medical

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