Publications by authors named "MinKang Guo"

4 Publications

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Exosomal miR-100-5p inhibits osteogenesis of hBMSCs and angiogenesis of HUVECs by suppressing the BMPR2/Smad1/5/9 signalling pathway.

Stem Cell Res Ther 2021 Jul 13;12(1):390. Epub 2021 Jul 13.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopaedic disease. Decreased osteogenesis and angiogenesis are considered the main factors in the pathogenesis of NONFH. We aimed to figure out whether exosomes and exosomal miRNA from necrotic bone tissues of patients with NONFH are involved in the pathogenesis of NONFH and reveal the underlying mechanisms.

Methods: RT-PCR and western blotting (WB) were used to detect the expression of osteogenic, adipogenic, and angiogenic markers. ALP staining and Alizarin Red S (ARS) staining were used to evaluate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to assess the adipocyte deposition. A tube formation assay was used to study angiogenesis of human umbilical vascular endothelial cells (HUVECs). H&E staining and immunohistochemistry (IHC) staining were used to detect the effect of the NONFH exosomes in vivo. MicroRNA sequencing was conducted to identify potential regulators in the NONFH exosomes. The target relationship between miR-100-5p and BMPR2 was predicted and confirmed by a dual luciferase reporter assay and WB.

Results: The NONFH exosomes reduced the osteogenic differentiation of hBMSCs and angiogenesis of HUVECs. In addition, the injection of the NONFH exosomes caused thinning and disruption of bone trabeculae in the femoral heads of rats. MiR-100-5p expression was upregulated in the NONFH exosomes and inhibited the osteogenesis of hBMSCs and angiogenesis of HUVECs by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway. Silencing miR-100-5p expression rescued the reduction in osteogenesis and angiogenesis caused by the NONFH exosomes by activating the BMPR2/SMAD1/5/9 signalling pathway.

Conclusion: The NONFH exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing the BMPR2/SMAD1/5/9 signalling pathway, which may be involved in the pathophysiological mechanisms of nontraumatic osteonecrosis of the femoral head (NONFH).
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http://dx.doi.org/10.1186/s13287-021-02438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278698PMC
July 2021

Malalignment sign on knee magnetic resonance imaging: a new predictor for excessive femoral anteversion in patients with patellar dislocation.

Knee Surg Sports Traumatol Arthrosc 2021 Apr 8;29(4):1075-1082. Epub 2020 Jun 8.

Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Purpose: To evaluate the clinical relevance of the newly identified malalignment sign in predicting excessive femoral anteversion in patients with patellar dislocations.

Methods: A total of 55 patients with patellar dislocation who underwent surgical treatment between 2016 and 2019 were included in this study. Femoral anteversion, tibial torsion, and the femorotibial index were measured via a CT scan. The malalignment sign on the knee MRI was defined as a malalignment between the lateral side of the intercondylar fossa of the femur and the lateral intercondylar eminence of the tibial plateau.

Results: A positive malalignment sign was observed in 36 of the 55 patients. Increased femoral anteversion was significantly correlated with the number of frames with a positive malalignment sign (r = 0.511, P < 0.001). The value of femoral anteversion was significantly greater in the group with a positive malalignment sign (P = 0.02). For a femoral anteversion value of 32°, the sensitivity and specificity of the malalignment sign reached the maximal level of 89.5% and 47.2%, respectively.

Conclusion: Increased femoral anteversion correlated significantly with a positive malalignment sign on knee MRI. However, tibial torsion did not affect the malalignment sign. A positive malalignment sign is evidence for femoral derotation osteotomy.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1007/s00167-020-06080-8DOI Listing
April 2021

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells.

Cell Death Dis 2020 04 27;11(4):293. Epub 2020 Apr 27.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFH-exos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.
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http://dx.doi.org/10.1038/s41419-020-2496-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184624PMC
April 2020

[Progranulin aggravates postmenopausal osteoporosis in ovariectomized mice].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019 Aug;35(8):714-720

Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. *Corresponding author, E-mail:

Objective To investigate the effect of progranulin (PGRN) on osteoporosis in ovariectomized mice. Methods PGRN-knockout (PGRN) and wild-type mice were ovariectomized to induce postmenopausal osteoporosis models. Next, the bone tissues in all mice were scanned by Micro-CT and three-dimensional reconstruction was performed to detect the micro-structure, followed by trabecula data analysis. The morphology and osteoclasts in the bone tissues of PGRN and wild-type mice were observed by HE staining and TRAP staining, respectively. The expression of receptor activator for nuclear factor-κB ligand (RANKL), tumor necrosis factor α (TNF-α) and P65 were detected by immunohistochemistry. The expression of TRAP mRNA in the mice was measured using fluorescence quantitative PCR and the protein expression of MMP9, MMP14, P65 was detected by Western blot analysis. Results Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) in the PGRN group were significantly higher than those in the wild-type group, while the trabecular separation (Tb.S) in the PGRN group was in the contrary. The degree of osteoporosis was less severe and number of osteoclasts in the PGRN mice were reduced, likewise, RANKL, TNF-α, MMP9, MMP14 and P65 as well as TRAP mRNA were down-regulated in the PGRN group compared with the wild-type group. Conclusion PGRN aggravates the postmenopausal osteoporosis in ovariectomized mice.
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August 2019
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