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Bone & Joint Research
Vol. 12, Issue 7 | Pages 397 - 411
3 Jul 2023
Ruan X Gu J Chen M Zhao F Aili M Zhang D

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 112 - 112
23 Feb 2023
Deng Y Zhang D Smith P Li R
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Hip and knee arthroplasty (HKA) are two of the most successful orthopaedic procedures. However, one major complication necessitating revision surgery is osteolysis causing aseptic loosening of the prosthesis. JAK-STAT has been demonstrated to influence bone metabolism and can be regulated by microRNA (miRNA).

Adult patients with osteolysis or aseptic loosening undergoing revision HKA were recruited. Age and gender matched patients undergoing primary hip or knee arthroplasty were our controls. Samples of bone, tissue and blood were collected and RNA isolation was performed. The best quality samples were used for RNA-sequencing. Data analysis was performed using RStudio and Galaxy to identify differentially expressed genes. Western blotting of IL6 was used to confirm protein expression.

Five circulating miRNA were identified which had 10 differentially expressed genes in bone and 11 differentially expressed genes in tissue related to the JAK-STAT pathway. IL6 in bone and EpoR in bone were highly significant and IL6 in tissue, MPL in bone, SOCS3 in tissue, JAK3 in bone and SPRED1 in bone were borderline significant. Western blot results demonstrated up-expression of IL6 in bone tissue of revision patients.

Periprosthetic osteolysis and aseptic loosening can be attributed to miRNA regulation of the JAK-STAT pathway in osteoblasts and osteoclasts, leading to increased bone resorption. These findings can be used for further experiments to determine utility in the clinical setting for identifying diagnostic markers or therapeutic targets.


Bone & Joint Research
Vol. 10, Issue 7 | Pages 411 - 424
14 Jul 2021
Zhao D Ren B Wang H Zhang X Yu M Cheng L Sang Y Cao S Thieringer FM Zhang D Wan Y Liu C

Aims

The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration.

Methods

IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 931 - 938
1 May 2021
Liu Y Lu H Xu H Xie W Chen X Fu Z Zhang D Jiang B

Aims

The morphology of medial malleolar fracture is highly variable and difficult to characterize without 3D reconstruction. There is also no universally accepeted classification system. Thus, we aimed to characterize fracture patterns of the medial malleolus and propose a classification scheme based on 3D CT reconstruction.

Methods

We retrospectively reviewed 537 consecutive cases of ankle fractures involving the medial malleolus treated in our institution. 3D fracture maps were produced by superimposing all the fracture lines onto a standard template. We sliced fracture fragments and the standard template based on selected sagittal and coronal planes to create 2D fracture maps, where angles α and β were measured. Angles α and β were defined as the acute angles formed by the fracture line and the horizontal line on the selected planes.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 492 - 499
1 Oct 2016
Li X Li M Lu J Hu Y Cui L Zhang D Yang Y

Objectives

To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention.

Materials and Methods

The study included 20 male Sprague-Dawley rats, ten in the young group (aged four to five weeks) and ten in the adult group (aged 18 to 20 weeks). In each rat, the upper-left first molar was subjected to a seven-day orthodontic force loading followed by a seven-day retention period. The upper-right first molar served as a control. The amount of orthodontic tooth movement was measured after seven-day force application and seven-day post-orthodontic retention. The expression levels of RANKL and the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were evaluated on day 7 (end of mechanical force loading) and day 14 (after seven days of post-orthodontic retention). Statistical analysis was performed using the t-test, and significance was set at p < 0.05.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 46 - 46
1 Jun 2012
Wise C Sharma S Gao X Londono D Mauldin KN Brandon J King V Zhang D Gordon D Herring J
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Introduction

Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility.

The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families.

Methods

We tested more than 327 000 single-nucleotide polymorphisms (SNPs) across all human autosomes for association with disease.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_III | Pages 446 - 446
1 Aug 2008
Gao X Herring J Cain N Gillum J Browne R Helms C Swaney S Zhang D Shoemaker S Lovett M Bowcock A Wise C
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Background and methods: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children, with a prevalence of 1–2%. The disease generally displays complex inheritance. Various family studies have produced many first reports of AIS susceptibility regions, but confirmation of these is lacking. In the present study we investigated extension of our own data, and reproducibility of other published results, by testing linkage in a new collection of fifty-four AIS families. Altogether fifteen candidate regions were evaluated in a two-stage design.

Results: Strongest results were obtained for linkage to microsatellite loci within a candidate region of proximal 8q previously identified by chromosomal breakpoint mapping. Although positive lod scores were obtained for other regions, none exhibited significance less than or equal to P = .05. Lod scores remained stable after analysis of an independent panel of SNP loci in the 8q candidate region and were strengthened with inclusion of additional affected family members (multipoint NPL = 3.02, P = 0.001). Two SNPs near the peak of linkage produced evidence of association to AIS susceptibility. Both SNPs are found within plausible candidate genes for AIS susceptibility.

Conclusion: These results support linkage of the 8q11-8q13 region to AIS susceptibility. Bashiardes et al. previously described a chromosomal break in the 8q11 region that disrupted the gamma-1- syntrophin (SNTG1) gene and segregated with AIS in an extended kindred. In that study, possible rare splice site mutations were identified an additional affected family and one sporadic case. The peak of linkage and association detected in this study appears to be distinct from the SNTG1 gene. This suggests the possibility that more than one gene in the region may contribute to disease. A more detailed analysis of the region encompassing this linkage peak, and the SNTG1 gene, is warranted in larger family collections.