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Bone & Joint Research
Vol. 12, Issue 7 | Pages 433 - 446
7 Jul 2023
Guo L Guo H Zhang Y Chen Z Sun J Wu G Wang Y Zhang Y Wei X Li P

Aims

To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis.

Methods

Empty adenovirus (EP) and a HDAC4 overexpression adenovirus were transfected into cultured human chondrocytes. The cell survival rate was examined by real-time cell analysis (RTCA) and EdU and flow cytometry assays. Cell biofunction was detected by Western blotting. The expression profiles of messenger RNAs (mRNAs) in the EP and HDAC4 transfection groups were assessed using whole-transcriptome sequencing (RNA-seq). Volcano plot, Gene Ontology, and pathway analyses were performed to identify differentially expressed genes (DEGs). For verification of the results, the A289E/S246/467/632 A sites of HDAC4 were mutated to enhance the function of HDAC4 by increasing HDAC4 expression in the nucleus. RNA-seq was performed to identify the molecular mechanism of HDAC4 in chondrocytes. Finally, the top ten DEGs associated with ribosomes were verified by quantitative polymerase chain reaction (QPCR) in chondrocytes, and the top gene was verified both in vitro and in vivo.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 82 - 89
1 Feb 2020
Chen Z Zhang Z Guo L Wei X Zhang Y Wang X Wei L

Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.

Cite this article: Bone Joint Res. 2020;9(2):82–89.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 475 - 475
1 Aug 2008
Liu T Chu WC Li K Yeung BH Guo L Man GC Lam WW Wong ST Cheng JC
Full Access

Aim: To investigate whether there is any difference in regional brain volumes between AIS patients and age matched, sex matched control subjects.

Method and Materials: 20 adolescent idiopathic scoliosis (AIS) female patients (age ranged from 11 yrs to 18 yrs, mean age of 14.5 yrs) and 20 sex matched, age matched controls have undergone MRI brain examination performed with a 1.5T scanner (Sonata, Siemens Medical Solutions, Erlanger, Germany). A Magnetization Preparation Rapid Acquisition Gradient Echo (MPR) sequence was used. Volumes of neuroanatomical regions were quantitated automatically by using whole brain segmentation technique of atlas-based hybrid warping. The whole brain was classified into 100 fine anatomical regions.

The results were taken as significant when p value was less than 0.05.

Results: Significant unilateral regional differences were found in the following regions:

Left thalamus and left postcentral gyrus of AIS patients were significantly larger than the control subjects. Anterior and posterior limb of right internal capsule, right caudate nucleus, right cuneus and left middle occipital gyurs of AIS patients were significantly smaller than the control subjects. Some regions were bilaterally involved: Perirhinal and hippocampus regions were larger in AIS while inferior occipital gyrus and precuneus were smaller than the corresponding regions in the control subjects. In the midline, the volumes of corpus callosum and brainstem in AIS patients were significantly larger than the control subjects.

Conclusion: Our study found that significant differences in particular regional brain volumes exist between AIS patients and the controls. Most of these regions involved the brain unilaterally, indicating that there might be abnormal asymmetrical development of the brain in AIS. This is the first study of its kind to show the presence of L-R asymmetry of regional brain volume difference in AIS patients as compared to normal controls. The findings might also help to explain the reported poor performance in the combined visual and proprioceptive test, spatial orientation test, abnormal nystagmus response to calorie test, and impaired postural balance in AIS patients.