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Aims

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing.

Methods

A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.


Bone & Joint Research
Vol. 10, Issue 12 | Pages 767 - 779
8 Dec 2021
Li Y Yang Y Wang M Zhang X Bai S Lu X Li Y Waldorff EI Zhang N Lee WY Li G

Aims

Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.

Methods

The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 41 - 50
1 Jan 2021
Wong RMY Choy VMH Li J Li TK Chim YN Li MCM Cheng JCY Leung K Chow SK Cheung WH

Aims

Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Methods

A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 857 - 869
1 Dec 2020
Slullitel PA Coutu D Buttaro MA Beaule PE Grammatopoulos G

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells.

Cite this article: Bone Joint Res 2020;9(12):857–869.


Objectives

MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.

Methods

Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 99 - 107
1 Mar 2020
Chang C Jou I Wu T Su F Tai T

Aims

Cigarette smoking has a negative impact on the skeletal system, causes a decrease in bone mass in both young and old patients, and is considered a risk factor for the development of osteoporosis. In addition, it disturbs the bone healing process and prolongs the healing time after fractures. The mechanisms by which cigarette smoking impairs fracture healing are not fully understood. There are few studies reporting the effects of cigarette smoking on new blood vessel formation during the early stage of fracture healing. We tested the hypothesis that cigarette smoke inhalation may suppress angiogenesis and delay fracture healing.

Methods

We established a custom-made chamber with airflow for rats to inhale cigarette smoke continuously, and tested our hypothesis using a femoral osteotomy model, radiograph and microCT imaging, and various biomechanical and biological tests.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 304 - 312
1 Jul 2019
Nicholson JA Tsang STJ MacGillivray TJ Perks F Simpson AHRW

Objectives

The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management.

Methods

A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 397 - 405
1 Jun 2018
Morcos MW Al-Jallad H Li J Farquharson C Millán JL Hamdy RC Murshed M

Objectives

Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of fracture callus in mice.

Methods

Tibial fractures were created and then stabilized in control wild-type (WT) and Phospho1-/- mice (n = 16 for each group; mixed gender, each group carrying equal number of male and female mice) at eight weeks of age. Fractures were allowed to heal for four weeks and then the mice were euthanized and their tibias analyzed using radiographs, micro-CT (μCT), histology, histomorphometry and three-point bending tests.