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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 36 - 36
19 Aug 2024
Ma C Goodnough LH Zhao L Chow SK Wang Y Chan CKF Goodman SB
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Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure.

We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities.

We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P<0.01), an effect not reversible even with the addition of BMP2.

Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 122 - 133
1 Feb 2021
He CP Jiang XC Chen C Zhang HB Cao WD Wu Q Ma C

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment.

Cite this article: Bone Joint Res 2021;10(2):122–133.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 689 - 700
7 Oct 2020
Zhang A Ma S Yuan L Wu S Liu S Wei X Chen L Ma C Zhao H

Aims

The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5).

Methods

TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 39 - 39
1 Aug 2020
Ma C Li C Jin Y Lu WW
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To explore a novel machine learning model to evaluate the vertebral fracture risk using Decision Tree model and train the model by Bone Mineral Density (BMD) of different compartments of vertebral body.

We collected a Computed Tomography image dataset, including 10 patients with osteoporotic fracture and 10 patients without osteoporotic fracture. 40 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients with osteoporotic fracture in the CT database and 53 non-fracture Vertebral bodies from T11 to L5 were segmented from 10 patients without osteoporotic fracture in the CT database. Based on the biomechanical properties, 93 vertebral bodies were further segmented into 11 compartments: eight trabecular bone, cortical shell, top and bottom endplate. BMD of these 11 compartments was calculated based on the HU value in CT images.

Decision tree model was used to build fracture prediction model, and Support Vector Machine was built as a compared model. All BMD data was shuffled to a random order. 70% of data was used as training data, and 30% left was used as test data. Then, training prediction accuracy and testing prediction accuracy were calculated separately in the two models.

The training accuracy of Decision Tree model is 100% and testing accuracy is 92.14% after trained by BMD data of 11 compartments of the vertebral body. The type I error is 7.14% and type II error is 0%. The training accuracy of Support Vector Machine model is 100% and the testing accuracy is 78.57%. The type I error is 17.86% and type II error is 3.57%.

The performance of vertebral body fracture prediction using Decision Tree is significantly higher than using Support Vector Machine. The Decision Tree model is a potential risk assessment method for clinical application. The pilot evidence showed that Decision Tree prediction model overcomes the overfitting drawback of Support Vector Machine Model. However, larger dataset and cohort study should be conducted for further evidence.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_IV | Pages 414 - 414
1 Apr 2004
Sinha R Ma C Esway J Crossett L
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Introduction: A 2-stage approach is often employed to treat infected TJA. Success rates have been reported between 85–100%. Other authors favor multiple routine debridements (I& D) to lower the infection rate. This study compares the relative effectiveness of 2-, 3- and 4 stage treatment approaches.

Methods: Between 1988 and 1998, all infected TJA at our institution were treated with a 2-, 3- or 4 stage approach. In the 2-stage approach, prosthesis removal was followed by 6 weeks of IV antibiotics and reimplantation. In the 3-stage approach, an additional I& D was added 5–7 days after prosthesis removal. In the 4-stage protocol, a third I& D was performed after completion of antibiotics. Negative cultures led to reimplantation. Positive cultures led to an additional 6-week course of antibiotics, and then repeat 3rd and 4th stages. Patients retained their components if free of infection, on chronic antibiotic suppression or after additional I& D. Patients were free of infection if no more treatment was needed.

Results: 83 patients with infected TJA were treated. Average follow-up was 25 months. Of the 2 stage patients, 9/10 (90%) retained their components, and 7/10 (70%) was free of infection. Of the 3 stage patients, 32/37 (86%) retained their components, and 28/37 (76%) was free of infection. Of the 4 stage patients, 34/36 (94%) retained their prosthesis, and 30/36 (83%) was free of infection. Seventeen additional patients in the 4-stage group had positive cultures at the third stage. After additional treatment 13/17 (76%) retained their components and 12/17 (71%) was free of infection. No correlation was found between infection severity (gram positive vs. negative organisms; single vs multiple organisms) or initial diagnosis.

Discussion. Our ten-year experience with infected THA suggests that multiple I& D are required for successful treatment. Repeat I& D assures a sterile wound, as tissue culture is more sensitive than aspiration. Importantly, persistent infection after three I& D and appropriate antibiotics led to poorer results, suggesting that other host factors may preclude these patients from reimplantation. Given the exorbitant costs of treating failed reimplantations, an additional routine I& D may in fact be cost-effective across an entire population of infected TJA patients. Further analysis will focus upon cemented versus cementless implants, cost-benefit ratios of multiple debridements, nutritional parameters, functional assessments of patients at latest follow-up, cost analysis, and the value of preoperative.

Conclusion: We recommend a 4-stage approach to the treatment of infected THA.