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Bone & Joint Research
Vol. 14, Issue 2 | Pages 124 - 135
20 Feb 2025
Huang J Zheng J Yin J Lin R Wu J Xu H Zhu J Zhang H Wang G Cai D

Aims

To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism.

Methods

Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 111 - 123
18 Feb 2025
Wang J Shan L Hang J Li H Meng Y Cao W Gu C Dai J Tao L

Aims

We aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis.

Methods

Postmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher’s discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 93 - 96
6 Feb 2025
Wignadasan W Fontalis A Shaeir M Haddad FS


Bone & Joint Research
Vol. 14, Issue 2 | Pages 97 - 110
6 Feb 2025
Zhang D Zhu T Bai J Chen C Wen J Zhou Y Guan X

Aims

In our previous research, we have found that melatonin (MEL) affects the osteoporotic process. By balancing bone remoulding, autophagy is involved in age-related bone loss. However, as a regulator of autophagy, whether MEL influences senile osteoporosis via regulating autophagy remains unclear.

Methods

Cellular, radiological, and histopathological evaluations were performed on 36 16-month-old male C57BL6/L mice or aged bone marrow-derived mesenchymal stem cells. A MEL-gelatin methacrylamide system was constructed to aid osteoporotic fracture healing.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 77 - 92
4 Feb 2025
Spanninga BJ Hoelen TA Johnson S Cheng B Blokhuis TJ Willems PC Arts JJC

Aims

Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system.

Methods

PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 69 - 76
1 Feb 2025
Tripon M Lalevee M van Rooij F Agu C Saffarini M Beaudet P

Aims

To evaluate how fore- and midfoot coronal plane alignment differs in feet with hallux valgus (HV), using 3DCT when measured in standard weightbearing (SWB) versus sesamoid view (SV) position, and to determine whether first metatarsophalangeal (MTP) dorsiflexion affects the relationship between the first metatarsal (M1) head and the sesamoid bones.

Methods

A consecutive series of 34 feet that underwent 3DCT in SWB and SV positions for symptomatic HV was assessed, of which four feet were excluded for distorted or incomplete images. Two foot and ankle clinicians independently digitized a series of points, and measured a series of angles according to a pre-defined protocol. Measurements include navicular pronation angle, M1 head (Saltzman angle), and metatarsosesamoid rotation angle (MSRA).


Bone & Joint Research
Vol. 14, Issue 1 | Pages 58 - 68
27 Jan 2025
Pelleg-Kallevag R Borgel S Kedar E Peled N May H

Aims

The development of lumbar lordosis has been traditionally examined using angular measurements of the spine to reflect its shape. While studies agree regarding the increase in the angles during growth, the growth rate is understudied, and sexual dimorphism is debated. In this study, we used a novel method to estimate the shape of the lumbar curve (LC) using the landmark-based geometric morphometric method to explore changes in LC during growth, examine the effect of size and sex on LC shape, and examine the associations between angular measurements and shape.

Methods

The study population included 258 children aged between 0 and 20 years (divided into five age groups) who underwent a CT scan between the years 2009 and 2019. The landmark-based geometric morphometric method was used to capture the LC shape in a sagittal view. Additionally, the lordosis was measured via Cobb and sacral slope angles. Multivariate and univariate statistical analyses were carried out to examine differences in shape between males and females and between the age groups.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 46 - 57
24 Jan 2025
Abdulhadi Alagha M Cobb J Liddle AD Malchau H Rolfson O Mohaddes M

Aims

While cementless fixation offers potential advantages over cemented fixation, such as a shorter operating time, concerns linger over its higher cost and increased risk of periprosthetic fractures. If the risk of fracture can be forecasted, it would aid the shared decision-making process related to cementless stems. Our study aimed to develop and validate predictive models of periprosthetic femoral fracture (PPFF) necessitating revision and reoperation after elective total hip arthroplasty (THA).

Methods

We included 154,519 primary elective THAs from the Swedish Arthroplasty Register (SAR), encompassing 21 patient-, surgical-, and implant-specific features, for model derivation and validation in predicting 30-day, 60-day, 90-day, and one-year revision and reoperation due to PPFF. Model performance was tested using the area under the curve (AUC), and feature importance was identified in the best-performing algorithm.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 42 - 45
21 Jan 2025
Fontalis A Wignadasan W Kayani B Haddad FS


Bone & Joint Research
Vol. 14, Issue 1 | Pages 33 - 41
17 Jan 2025
Fujimoto K Kanamoto T Otani S Miyazaki R Ebina K Nakata K

Aims

Ultrasound-guided injection techniques are expected to enhance therapeutic efficacy for skeletal muscle injuries and disorders, but basic knowledge is lacking. The purpose of this study was to examine the diagnostic accuracy of ultrasound for abnormal skeletal muscle lesions, and to examine the distribution patterns of solution and cells injected into abnormal muscle lesions under ultrasound guidance.

Methods

A cardiotoxin (CTX)-induced muscle injury model was used. Briefly, CTX was injected into tibialis anterior muscle in rats under ultrasound observation. First, the diagnostic accuracy of abnormal muscle lesions on ultrasound was examined by comparing ultrasound findings and histology. Next, Fast Green solution and green fluorescent protein (GFP)-labelled cells were simultaneously injected into the abnormal muscle lesions under ultrasound guidance, and their distribution was evaluated.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 20 - 32
17 Jan 2025
Chen Z Zhou T Yin Z Duan P Zhang Y Feng Y Shi R Xu Y Pang R Tan H

Aims. Magnesium ions (Mg. 2+. ) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg. 2+. combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg. 2+. in cartilage repair. Methods. A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg. 2+. treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg. 2+. was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results. The histological results showed that the 0.5 mol/L Mg. 2+. group had deeper positive staining in haematoxylin-eosin (H&E), safranin O, Alcian blue, and type II collagen staining. The new cartilage coverage in the injury area was more complete, and the regeneration of hyaline cartilage was higher. The RT-qPCR results showed that sirtuin 1/bone morphogenetic protein-2/sex-determining region Y box 9 (SIRT1/BMP-2/SOX-9) and hypoxia-inducible factor 1-alpha (HIF-1α) messenger RNA levels were up-regulated after Mg. 2+. injection. Conclusion. MFX combined with Mg. 2+. treatment has a positive effect on cartilage repair. The Mg. 2+. injection dose of 0.5 mol/L is most effective in enhancing microfracture-mediated cartilage repair. Cite this article: Bone Joint Res 2025;14(1):20–32


Bone & Joint Research
Vol. 14, Issue 1 | Pages 16 - 19
15 Jan 2025
Jones S Tyson S


Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims

The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.

Methods

Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 764 - 778
12 Dec 2024
Huang Q Zhuo Y Duan Z Long Y Wang J Zhang Z Fan S Huang Y Deng K Xin H

Aims. Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion. Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777


Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims. This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults. Methods. The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023. Results. The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC. Conclusion. This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC. Cite this article: Bone Joint Res 2024;13(12):750–763


Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 716 - 724
4 Dec 2024
Cao S Chen Y Zhu Y Jiang S Yu Y Wang X Wang C Ma X

Aims. This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation. Methods. A total of 16 subjects with CAI (eight without OLT and eight with OLT) and eight healthy subjects underwent gait analysis in a stair descent setting. Inverse dynamic analysis was applied to ground reaction forces and marker trajectories using the AnyBody Modeling System. One-dimensional statistical parametric mapping was performed to compare ankle joint reaction force and joint moment curve among groups. Results. The patients with OLT showed significantly increased dorsiflexion moment in the ankle joint compared with healthy subjects during 38.2% to 40.9% of the gait cycle, and increased eversion moment in the ankle joint compared with patients without OLT during 25.5% to 27.6% of the gait cycle. Compared with healthy subjects, the patients with OLT showed increased anterior force during 42% to 43% of the gait cycle, and maximal medial force (p = 0.005, ηp2 = 0.399). Conclusion. The patients with concomitant CAI and OLT exhibit increased dorsiflexion and eversion moment, as well as increased anterior and medial ankle joint reaction force during stair descent, compared with patients with CAI but without OLT and healthy subjects, respectively. Thus, a rehabilitative regimen targeting excessive ankle dorsiflexion and eversion moment may help to reduce ankle joint loading. Cite this article: Bone Joint Res 2024;13(12):716–724


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Methods

A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 673 - 681
22 Nov 2024
Yue C Xue Z Cheng Y Sun C Liu Y Xu B Guo J

Aims

Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH.

Methods

This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.