Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

doi:10.1038/ncomms10872

. 2016 Mar 7:7:10872.

doi: 10.1038/ncomms10872.

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

Defang Li^{1

2

3

4

5}, Jin Liu^{1

2

3

4}, Baosheng Guo^{1

2

3

4

5

6}, Chao Liang^{1

2

3

4

7

8}, Lei Dang^{1

2

3

4}, Cheng Lu^{2

9}, Xiaojuan He^{1

9}, Hilda Yeuk-Siu Cheung^{1

6}, Liang Xu¹, Changwei Lu¹, Bing He^{1

2

3

4}, Biao Liu^{1

2

3

4

6}, Atik Badshah Shaikh^{1

2

3

4}, Fangfei Li^{1

2

3

4}, Luyao Wang^{1

2

3

4}, Zhijun Yang^{1

2

3

4

6}, Doris Wai-Ting Au¹⁰, Songlin Peng^{1

11}, Zongkang Zhang¹², Bao-Ting Zhang¹², Xiaohua Pan^{1

13}, Airong Qian^{8

14}, Peng Shang^{8

14}, Lianbo Xiao^{1

15}, Baohong Jiang¹⁶, Chris Kong-Chu Wong¹⁷, Jiake Xu¹⁸, Zhaoxiang Bian^{1

2

3}, Zicai Liang⁴, De-An Guo¹⁶, Hailong Zhu^{1

2

3

4}, Weihong Tan⁷, Aiping Lu^{1

2

3

4

5

6

7

8

9

15}, Ge Zhang^{1

2

3

4

5

6

7

8

15}

Affiliations

¹ Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
² Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
³ Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.
⁴ Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
⁵ Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.
⁶ Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
⁷ Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.
⁸ Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.
⁹ Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
¹⁰ Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR 999077, China.
¹¹ Department of Spine Surgery, Shenzhen People's Hospital, Ji Nan University Second College of Medicine, Shenzhen 518020, China.
¹² School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR 999077, China.
¹³ Department of Orthopaedics and Traumatology, Bao'an Hospital Affiliated to Southern Medical University and Shenzhen 8th People Hospital, Shenzhen 518100, China.
¹⁴ Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.
¹⁵ Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
¹⁶ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
¹⁷ Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China.
¹⁸ Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6907, Australia.

PMID: 26947250
PMCID: PMC4786676
DOI: 10.1038/ncomms10872

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

Defang Li et al. Nat Commun. 2016.

. 2016 Mar 7:7:10872.

doi: 10.1038/ncomms10872.

Authors

Affiliations

¹ Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
² Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR 999077, China.
³ Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery, HKBU Institute of Research and Continuing Education, Shenzhen 518057, China.
⁴ Research Group of Bone and Joint Diseases, HKBU Institute of Science and Technology, Haimen 226100, China.
⁵ Academician Chen Xinzi Workroom for Advancing Translational Medicine in Bone and Joint Diseases, Kunshan RNAi Institute, Kunshan Industrial Technology Research Institute, Kunshan, Jiangsu 215300, China.
⁶ Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR 999077, China.
⁷ Hong Kong Baptist University Branch of State Key Laboratory of Chemo/Biosensing and Chemometrics of Hunan University, Hong Kong 999077, China.
⁸ Hong Kong Baptist University-Northwestern Polytechnical University Joint Research Centre for Translational Medicine on Musculoskeletal Health in Space, Shenzhen 518057, China.
⁹ Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
¹⁰ Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR 999077, China.
¹¹ Department of Spine Surgery, Shenzhen People's Hospital, Ji Nan University Second College of Medicine, Shenzhen 518020, China.
¹² School of Chinese Medicine, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR 999077, China.
¹³ Department of Orthopaedics and Traumatology, Bao'an Hospital Affiliated to Southern Medical University and Shenzhen 8th People Hospital, Shenzhen 518100, China.
¹⁴ Key Laboratory for Space Bioscience and Biotechnology, Institute of Special Environmental Biophysics, School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.
¹⁵ Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai 200052, China.
¹⁶ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
¹⁷ Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China.
¹⁸ Molecular Laboratory, School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia 6907, Australia.

PMID: 26947250
PMCID: PMC4786676
DOI: 10.1038/ncomms10872

Abstract

Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-3p associates with both elevated serum exosomal miR-214-3p and reduced bone formation in elderly women with fractures and in ovariectomized (OVX) mice. Osteoclast-specific miR-214-3p knock-in mice have elevated serum exosomal miR-214-3p and reduced bone formation that is rescued by osteoclast-targeted antagomir-214-3p treatment. We further demonstrate that osteoclast-derived exosomal miR-214-3p is transferred to osteoblasts to inhibit osteoblast activity in vitro and reduce bone formation in vivo. Moreover, osteoclast-targeted miR-214-3p inhibition promotes bone formation in ageing OVX mice. Collectively, our results suggest that osteoclast-derived exosomal miR-214-3p transfers to osteoblasts to inhibit bone formation. Inhibition of miR-214-3p in osteoclasts may be a strategy for treating skeletal disorders involving a reduction in bone formation.

PubMed Disclaimer

Figures

**Figure 1. Increased intraosseous miR-214-3p associates with elevated serum exosomal miR-214-3p and reduced bone formation in elderly patients.**
(a) A schematic diagram illustrating the experimental design. Serum and bone samples were collected from elderly woman patients with or without fractures, and divided into 60–69, 70–79 and 80–89 groups, respectively, according to age. (b) Real-time PCR analysis of the age-related changes in miR-214-3p levels in whole serum (left), serum exosomes (middle) and bone specimens (right) from elderly patients with or without fractures, respectively. The relative miR-214-3p level in each group was normalized to the mean value of the 60–69 group. Human RUN6B was used as the internal control. All data are the mean±s.d. *P<0.05, **P<0.01. Two-way analysis of variance (ANOVA) with a *Turkey's* multiple comparisons test was performed. Both the time effect (age), the group effect (with or without fractures) and the time-by-group interaction effect were all statistically significant for all the examined parameters. (c) Real-time PCR analysis showing the age-related changes in *BGLAP* mRNA levels in bone specimens from elderly patients with fractures, respectively. The relative *BGLAP* mRNA level in each group was normalized to the mean value of the 60–69 group. Human *GAPDH* mRNA was used as the internal control. Data are the mean±s.d. **P<0.01. One-way ANOVA with a *post-hoc* test was performed. (d) Western blot analysis of the osteoclast marker proteins (CTSK, TRAcP5 and Sema4D) in the lysates of serum exosomes isolated from elderly patients with or without fractures. OCs, the lysates of osteoclasts differentiated from human peripheral blood mononuclear cells. Exo 1, the lysates of serum exosomes from elderly patients without fractures. Exo 2, the lysates of serum exosomes from elderly patients with fracture. (e) Correlation analysis between exosomal and intra-osseous miR-214-3p levels (left), between exosomal miR-214-3p level and intra-osseous *BGLAP* mRNA level (middle) and between intra-osseous miR-214-3p level and intra-osseous *BGLAP* mRNA level (right), respectively, in elderly patients with fractures. The n value for each group is indicated at the bottom of each histogram.

**Figure 2. Increased intra-osteoclast miR-214-3p associates with elevated serum exosomal miR-214-3p and reduced bone formation in OVX mice.**
(a) A schematic diagram illustrating the experimental design. Serum and bone samples were collected from female C57BL/6 mice that were ovariectomized at 6-month-old and killed at 6 months (as baseline, OVX-6mon-BS), 9 months (OVX-9mon) and 12 months (OVX-12mon) after ovariectomy, respectively. (b) Real-time PCR analysis of the age-related changes in the levels of miR-214-3p in whole serum (left) and serum exosomes (middle left), and the levels of pri-miR-214-3p (middle), pre-miR-214-3p (middle right) and mature miR-214-3p in osteoclasts (right) in OVX mice in three age-subgroups, respectively. The relative miR-214-3p level in each group was normalized to the mean value of the OVX-BS group. Mouse snoRNA-202 was used as the internal control. (c) Representative images of new bone formation at distal femur metaphysis assessed by double labelling with calcein green and xylenol orange in three age-subgroups. Scale bar, 10 μm. (d) Bone histomorphometry analysis of the age-related changes in BFR/BS at distal femur in three age-subgroups, respectively. (e) Correlation analysis between serum exosomal miR-214-3p level and BFR/BS (left), between serum exosomal and intraosteoclast miR-214-3p levels (middle) and between intraosteoclast miR-214-3p level and BFR/BS (right), respectively. The n value for each group is indicated at the bottom of each histogram. All data are the mean±s.d. **P<0.01. One-way ANOVA with a *post-hoc* test was performed.

**Figure 3. Reduced bone formation in OC-miR-214-3p mice.**
(a) A schematic diagram illustrating the experimental design. (b,c) Schematic diagrams of the development strategy of the OC-miR-214-3p mice. The ROSA26-miR-214-3p knock-in mice containing the miR-214-3p knock-in allele were generated, and then crossed with the *Ctsk-cre* transgenic mice to obtain the OC-miR-214-3p mice. One unit included the mmu-miR-214-3p stem–loop, a 200-bp 5′ flanking sequence and a 200-bp 3′ flanking sequence. (d) Real-time PCR analysis of pri-miR-214-3p (left), pre-miR-214-3p (middle left) and miR-214-3p (middle right) levels in osteoclasts (OCs) versus non-osteoclasts (non-OCs) and serum exosomal miR-214-3p level (right) from WT and OC-miR-214-3p mice. The OCs and non-OCs were the Ctsk⁺ and Ctsk⁻ cells isolated from the bone marrow cells by magnetic-activated cell sorting, respectively. (e) Real-time PCR analysis of the mRNA levels of bone formation marker genes (*Alp*, *Opn*, *BSP* and *Bglap*) in bone specimens from WT and OC-miR-214-3p mice. (f) Representative micro-CT images of the distal femur from WT and OC-miR-214-3p mice. (g) The values of micro-CT parameters (BMD, BV/TV, Tb.Th and Tb.N) at the distal femur metaphysis from WT and OC-miR-214-3p mice. (h) Representative images of new bone formation assessed by double labelling with calcein green and xylenol orange at the cortical bone (CB) and trabecular bone (TB) of distal femur from WT and OC-miR-214-3p mice. Scale bars, 10 μm. (i) The values of bone histomorphometry parameters (MAR, BFR/BS, Ob.S/BS, Ob.N/B.Pm, Oc.S/BS and Oc.N/B.Pm) at the distal femur metaphysis from WT and OC-miR-214-3p mice. (j) Representative images of osteoid formation indicated by Masson's trichrome staining at the distal femur metaphysis of WT and OC-miR-214-3p mice. Scale bars, 20 μm. (k) The values of osteoid-related parameters (Osteoid surface/bone surface and Osteoid thickness) at the distal femur metaphysis from WT and OC-miR-214-3p mice. The n value for each group is indicated at the bottom of each histogram. All data are the mean±s.d. *P<0.05 versus WT. **P<0.01 versus WT. Student's t-test was performed.

**Figure 4. Osteoclast-targeted antagomir-214-3p treatment rescues bone phenotype in OC-miR-214-3p mice.**
(a) A schematic diagram illustrating the experimental design. The 4-week-old OC-miR-214-3p or WT mice were intravenously injected with PBS (OC214-3p/WT), (D-Asp)₈-liposome (vehicle) alone (OC214-3p+Veh/WT+Veh), (D-Asp)₈-liposome-antagomir nonsense control (OC214-3p+NC/WT+NC) and (D-Asp)₈-liposome-antagomir-214-3p (OC214-3p+AMO/WT+AMO), respectively, at a weekly interval and killed 4 weeks after the first treatment. Another group of OC-miR-214-3p or WT mice were killed at 4-week-old before treatment initiation as baseline (OC214-3p-BS/WT-BS). (b) Representative micro-CT images of the distal femur metaphysis in each group. Scale bars, 1 mm. (c) The values of micro-CT parameter (BMD) at the distal femur metaphysis in each group. (d) Representative images of new bone formation assessed by double labelling with calcein green and xylenol orange at the distal femur metaphysis in each group. Scale bars, 10 μm. (e) The values of bone histomorphometry parameter (BFR/BS) at the distal femur metaphysis in each group. The n value for each group is indicated at the bottom of each histogram. All data are the mean±s.d. *P<0.05. NS, not significant. One-way ANOVA with a *post-hoc* test was performed.

**Figure 5. Osteoclastic miR-214-3p inhibit osteoblast activity.**
(a) A schematic diagram illustrating the design of the co-culture experiments. The osteoblasts derived from the calvarial bone of newborn C57BL/6 mice were co-cultured with the osteoclasts derived from OC-miR-214-3p mice (OC-miR-214-3p OCs) or WT mice (WT OCs), or cultured without osteoclasts (No OC). (b) Real-time PCR analysis of the supernatant, supernatant exosomal and intra-osteoblast miR-214-3p levels (normalized by the mean value of No OC) at 24 h after co-culture, respectively. (c) The pri-miR-214-3p and pre-miR-214-3p levels in osteoblasts at 24 h after co-culture. (d) Real-time PCR analysis of the mRNA levels of osteoblast activity-related marker genes (*Alp*, *Opn*, *BSP* and *Bglap*) in osteoblasts at 48 h after co-culture. (e) Real-time PCR analysis of the mRNA expression levels of *Alp*, *Opn*, *BSP* and *Bglap* in osteoblasts transfected with exogenous ATF4 mRNA 3′UTR at 48 h after co-culture. The osteoblasts transfected with either vehicle (OC-miR-214 3p+Veh), nonsense 3′UTR control (OC-miR-214 3p+NC) or ATF4 mRNA 3′UTR (OC-miR-214 3p+ ATF4 mRNA 3′UTR) were co-cultured with the OC-miR-214 3p osteoclasts. All data are the mean±s.d. of four independent experiments. *P<0.05. One-way ANOVA with a *post-hoc* test was performed.

**Figure 6. Osteoclast-derived exosomal miR-214-3p transfer to osteoblasts.**
(a) A schematic diagram illustrating the design of co-culture experiments with GFP-exosome-producing osteoclasts and osteoblasts. CMV-GFP-CD63 were transfected into the OC-miR-214-3p osteoclasts to label the osteoclast-derived exosomes. (b) Representative confocal images of the GFP-exosome-producing osteoclasts at 24 h after transfection (left panels), and the uptake of GFP-exosome by osteoblasts (right panels) at 24 h after co-culture. (c) A schematic diagram illustrating the design of co-culture experiments with the osteoblasts and *miR-214-3p*-depleted osteoclasts (upper panels), and real-time PCR analysis of the levels of pri-miR-214-3p, pre-miR-214-3p and miR-214-3p in osteoblasts (normalized by the mean value of No OC group) at 24 h after co-culture with *miR-214-3p*-depleted/intact osteoclasts differentiated from *miR-214-3p*-depleted/intact RAW264.7 cells, respectively (lower panels). (d) A schematic diagram illustrating the design of co-culture experiments with the osteoclasts and *miR-214-3p*-depleted osteoblasts (upper panels), and real-time PCR analysis of the miR-214-3p level in *miR-214-3p*-depleted osteoblasts (normalized by the mean value of No OC group) at 24 h after co-culture with either OC-miR-214-3p or WT osteoclasts (lower panels). All data are the mean±s.d. of four independent experiments. *P<0.05. One-way ANOVA with a *post-hoc* test was performed.

**Figure 7. Osteoclast-derived exosomes target osteoblasts.**
(a) Representative biophotonic images of the tissue distribution of fluorescence signal in mice at 4 and 8 h after intravenous injection of purified PKH67-labelled exosomes isolated from the supernatant of OC-miR-214-3p osteoclasts (OC-Exo). (b) Representative biophotonic images of the tissue distribution of fluorescence signal in mice at 8 h after intravenous injection of purified PKH67 exosomes isolated from the supernatant of either OC-miR-214-3p osteoclast (OC-Exo) or HEK 293T cells (HEK-Exo). (c) Western blot analysis of the Sema4D protein expression in pellets of sucrose gradient fractions from the osteoclast-derived exosome preparations. The density of each fraction was determined by refraction index measurements. (d,e) Flow cytometry analysis of PKH67⁺ osteoblasts after incubation with PKH67-labelled exosomes derived from OC-miR-214-3p osteoclasts. The PKH67-labelled exosomes were pre-treated with either anti-Sema4D (20 μg ml⁻¹) or isotype-matched control (Sema4D iso) and then added to osteoblasts for 4 h incubation. (f) Real-time PCR analysis of the levels of pri-miR-214, pre-miR-214 and mature miR-214 in osteoblasts after incubation with either anti-Sema4D-treated exosomes (OC Exo+Anti-Sema4D) or Sema4D isotype-treated exosomes (OC Exo+Sema4D iso), respectively. All data are the mean±s.d. of four independent experiments. *P<0.05. One-way ANOVA with a *post-hoc* test was performed.

**Figure 8. Osteoclast-derived exosomal miR-214-3p inhibit bone formation.**
(a) A schematic diagram illustrating the experimental design. The female C57BL/6 mice were intravenously injected with purified exosomes derived from either OC-miR-214-3p (OC-miR-214-3p Exo) or WT (WT-Exo) osteoclasts. (b) Real-time PCR analysis of the levels of either pri-miR-214, pre-miR-214 or miR-214 in ALP⁺ cells (osteoblasts) isolated from bone marrow cells by fluorescence-activated cell sorting at 24 h after the mice were intravenously injected with either OC-miR-214-3p Exo or WT-Exo. (c) Real-time PCR analysis of the mRNA expression levels of *Alp*, *Opn*, *BSP* and *Bglap* in femurs from the mice administered with either OC-miR-214-3p Exo or WT-Exo, respectively. (d) Representative micro-CT images of the distal femur metaphysis from the mice administered with either OC-miR-214-3p Exo or WT-Exo. Scale bar, 1 mm. (e) The values of micro-CT parameters (BMD, BV/TV, Tb.Th and Tb.N) at the distal femur metaphysis from the mice administered with either OC-miR-214-3p Exo or WT-Exo, respectively. (f) Representative images of new bone formation assessed by double labelling with calcein green and xylenol orange at the distal femur metaphysis from the mice administered with either OC-miR-214-3p Exo or WT-Exo. Scale bars, 10 μm. (g) The values of bone histomorphometry parameters (MAR, BFR/BS, Ob.S/BS, Ob.N/B.Pm) at the distal femur metaphysis from the mice administered with either OC-miR-214-3p Exo or WT-Exo, respectively. The n value for each group is indicated at the top/bottom of each histogram. All data are the mean±s.d. *P<0.05 versus WT. Student's t-test was performed.

**Figure 9. Osteoclast-targeted antagomiR-214-3p treatment promotes bone formation in ageing OVX mice.**
(a) A schematic diagram illustrating the experimental design. The female C57BL/6 mice were either ovariectomized or Sham operated at 6-month-old, and left untreated for 6 months. At 12-month-old, the OVX mice received eight consecutive intravenous injections with either PBS (OVX), (D-Asp)8-liposome (vehicle) alone (OVX+Veh), (D-Asp)8-liposome-antagomir nonsense control (OVX+NC) or (D-Asp)8-liposome-antagomir-214-3p (OVX+AMO), whereas the Sham mice received eight consecutive intravenous injections with PBS (Sham), at a weekly interval and killed 8 weeks after the first injection. Another group of OVX mice were killed at 12-month-old before treatment initiation as baseline (OVX-BS). (b) Real–time PCR analysis of the miR-214-3p levels in CTSK⁺ cells (Osteoclasts) and ALP⁺ cells (osteoblasts) isolated from cryosections of femur by laser-captured microdissection from the mice in each group. (c) Representative micro-CT images of the distal femur metaphysis from the mice in each group. Scale bars, 1 mm. (d) The values of micro-CT parameters (BMD, BV/TV, Tb.Th and Tb.N) at the distal femur metaphysis from the mice in each group. (e) Representative images of new bone formation assessed by double labelling with calcein green and xylenol orange at the distal femur metaphysis from the mice in each group. Scale bars, 10 μm. (f) The values of bone histomorphometry parameters (MAR, BFR/BS) at the distal femur metaphysis from the mice in each group. The n value for each group is indicated at the top/bottom of each histogram. All data are the mean±s.d. *P<0.05. One-way ANOVA with a *post-hoc* test was performed.

See this image and copyright information in PMC

Cited by

Urine-derived extracellular vesicle miRNAs as possible biomarkers for and mediators of necrotizing enterocolitis: A proof of concept study.
Galley JD, Mar P, Wang Y, Han R, Rajab A, Besner GE. Galley JD, et al. J Pediatr Surg. 2021 Nov;56(11):1966-1975. doi: 10.1016/j.jpedsurg.2021.02.016. Epub 2021 Mar 2. J Pediatr Surg. 2021. PMID: 33785202 Free PMC article.
Serum miRNA-142 and BMP-2 are markers of recovery following hip replacement surgery for femoral neck fracture.
Gao H, Wang X. Gao H, et al. Exp Ther Med. 2020 Nov;20(5):105. doi: 10.3892/etm.2020.9235. Epub 2020 Sep 18. Exp Ther Med. 2020. PMID: 32989384 Free PMC article.
A bimolecular modification strategy for developing long-lasting bone anabolic aptamer.
Zhang H, Yu S, Ni S, Gubu A, Ma Y, Zhang Y, Li H, Wang Y, Wang L, Zhang Z, Yu Y, Lyu A, Zhang B, Zhang G. Zhang H, et al. Mol Ther Nucleic Acids. 2023 Nov 10;34:102073. doi: 10.1016/j.omtn.2023.102073. eCollection 2023 Dec 12. Mol Ther Nucleic Acids. 2023. PMID: 38074899 Free PMC article.
Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone.
Cottone L, Ligammari L, Lee HM, Knowles HJ, Henderson S, Bianco S, Davies C, Strauss S, Amary F, Leite AP, Tirabosco R, Haendler K, Schultze JL, Herrero J, O'Donnell P, Grigoriadis AE, Salomoni P, Flanagan AM. Cottone L, et al. Cell Death Differ. 2022 Dec;29(12):2459-2471. doi: 10.1038/s41418-022-01031-x. Epub 2022 Aug 3. Cell Death Differ. 2022. PMID: 36138226 Free PMC article.
Down-expression of miR-494-3p in senescent osteocyte-derived exosomes inhibits osteogenesis and accelerates age-related bone loss via PTEN/PI3K/AKT pathway.
Yao C, Sun J, Luo W, Chen H, Chen T, Chen C, Zhang B, Zhang Y. Yao C, et al. Bone Joint Res. 2024 Feb 1;13(2):52-65. doi: 10.1302/2046-3758.132.BJR-2023-0146.R2. Bone Joint Res. 2024. PMID: 38295830 Free PMC article.

See all "Cited by" articles

References

1. Sims N. A. & Martin T. J. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. BoneKEy Rep. 3, 481 (2014). - PMC - PubMed
1. Rachner T. D., Khosla S. & Hofbauer L. C. Osteoporosis: now and the future. Lancet 377, 1276–1287 (2011). - PMC - PubMed
1. Zaidi M. Skeletal remodeling in health and disease. Nature Med. 13, 791–801 (2007). - PubMed
1. Martin T. J. & Sims N. A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med. 11, 76–81 (2005). - PubMed
1. Irie N. et al. Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J. Biol. Chem. 284, 14637–14644 (2009). - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- MedlinePlus Health Information
Molecular Biology Databases
- Mouse Genome Informatics (MGI)

[1] Sims N. A. & Martin T. J. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. BoneKEy Rep. 3, 481 (2014). - PMC - PubMed

[2] Sims N. A. & Martin T. J. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. BoneKEy Rep. 3, 481 (2014). - PMC - PubMed

[3] Rachner T. D., Khosla S. & Hofbauer L. C. Osteoporosis: now and the future. Lancet 377, 1276–1287 (2011). - PMC - PubMed

[4] Rachner T. D., Khosla S. & Hofbauer L. C. Osteoporosis: now and the future. Lancet 377, 1276–1287 (2011). - PMC - PubMed

[5] Zaidi M. Skeletal remodeling in health and disease. Nature Med. 13, 791–801 (2007). - PubMed

[6] Zaidi M. Skeletal remodeling in health and disease. Nature Med. 13, 791–801 (2007). - PubMed

[7] Martin T. J. & Sims N. A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med. 11, 76–81 (2005). - PubMed

[8] Martin T. J. & Sims N. A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol. Med. 11, 76–81 (2005). - PubMed

[9] Irie N. et al. Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J. Biol. Chem. 284, 14637–14644 (2009). - PMC - PubMed

[10] Irie N. et al. Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J. Biol. Chem. 284, 14637–14644 (2009). - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

Affiliations

Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Abstract

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases