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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


Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

Aims

Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Methods

A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

Methods

A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 147 - 154
20 Feb 2023
Jia Y Qi X Ma M Cheng S Cheng B Liang C Guo X Zhang F

Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Methods

We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects.


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. 10, Issue 8 | Pages 514 - 525
2 Aug 2021
Chen C Kang L Chang L Cheng T Lin S Wu S Lin Y Chuang S Lee T Chang J Ho M

Aims

Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model.

Methods

Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 578 - 586
1 Sep 2020
Ma M Liang X Wang X Zhang L Cheng S Guo X Zhang F Wen Y

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Methods

The articular cartilage specimens were collected from five KBD patients and five control subjects for cell culture. The messenger RNA (mRNA) and protein expression levels were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot. The survival rate of C28/I2 chondrocyte cell line was detected by MTT assay after T-2 toxin intervention. The cell viability and mRNA expression levels of apoptosis related genes between COMP-overexpression groups and control groups were examined after cell transfection.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 290 - 303
1 Jul 2019
Li H Yang HH Sun ZG Tang HB Min JK

Objectives

The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).

Methods

The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo.