Journal of Orthopaedic Research®最新文献

Lane and Sandhu introduced a radiological score to evaluate bone union in animal and human models after experimental bone grafting. We introduce an extension of the Lane and Sandhu Scoring system to serve as a more granular system for robust bone healing assessment in clinical research. We describe the application of this scoring system in the context of an autologous cell-based osteogenic implant (NVD003) designed to improve the rate of bone union. Images from four participants with congenital pseudoarthrosis of the tibia (CPT) and 9 adults with recurrent osseous non-union after conventional surgery were obtained. All participants underwent NVD003 implantation. An extended version of the Lane and Sandhu scoring system (eLSS; range from 0 to 12) was employed to assess bone formation, union, and remodeling by two independent readers longitudinally, with final adjudication in cases of > 1 point disagreement. Interobserver agreement was assessed using quadratic weighted kappa. 206 exams (170 radiographs and 36 CT scans) were studied across the two pathologies (81 scans for participants with CPT and 125 scans for participants with recurrent osseous non-union). Overall agreement between the expert readers was found to be 0.84 (95% CI: 0.79, 0.89), with comparable agreement found per modality (radiographs [0.85] and CT images [0.76]) and per pathology (CPT [0.83] and recurrent osseous non-union [0.84]). These results support that the eLSS has sufficient reliability to warrant further consideration for clinical trial use. Additional studies with a greater number of subjects, raters, and variety of use cases are required to validate and optimize this method.

Level of Evidence: III

Diffusion tensor imaging (DTI) has exhibited remarkable success in probing the tissue microstructure of connective tissues. How the different DTI metrics correlate to molecular and structural changes in osteoarthritis (OA) has not been thoroughly investigated. The potential of DTI to evaluate the 3D collagen fiber network in osteoarthritic cartilage remains largely unexplored. This study aims to assess tissue microstructure and 3D collagen fiber alterations following destabilization of the medial meniscus (DMM) surgery in rats using high-resolution DTI. MRI scans were conducted on 8 DMM and 8 SHAM knee joints. A 3D diffusion-weighted spin-echo pulse sequence, incorporating undersampling in both phase dimensions, was employed at 9.4 T. The fractional anisotropy (FA) values were significantly decreased in femoral cartilage in the DMM group, while the mean diffusivity (MD) and radial diffusivity (RD) values in both femoral and tibial cartilage were significantly increased. Regional analysis of femoral cartilage revealed that these differences were more pronounced in the anterior and central areas. Tractography provided evidence of disrupted 3D collagen fiber architecture in the DMM group. Simulations were conducted in the extra-collagen space with and without collagen dispersion/disruption, and with and without glycosaminoglycans (GAG), to interpret the DTI results. The simulations revealed that the loss of GAG primarily led to increased MD, while collagen dispersion/disruption predominantly resulted in decreased FA. Imaging and simulation findings were supported by changes on histology. High-resolution DTI enables visualization of 3D collagen fiber architecture and detection of changes in cartilage tissue integrity, which are crucial for understanding cartilage degradation in OA.

Rotator cuff tendon injuries are common, particularly among the elderly. However, promising biomarkers to assess tendon degeneration and healing remain limited. This study aimed to identify dynamic biomarkers by analyzing temporal gene expression and histological changes in a chronic rotator cuff tear model. Using Sprague–Dawley rats, a chronic injury was induced by detaching the supraspinatus tendon and inserting a silastic drain to inhibit spontaneous healing. Tendon samples were collected at multiple time points after injury and after repair for gene expression profiling and histological analysis. Human supraspinatus tendon samples (normal and degenerative) were acquired for validation. A three-dimensional in vitro tendon construct model using human adipose-derived stem cells was subjected to mechanical loading to investigate gene expression under controlled conditions. Tendon-specific markers, including Scleraxis, Tenascin C, and Collagen III, were downregulated early after injury but demonstrated partial recovery with scar formation, limiting their utility as healing indicators. Conversely, Collagen I and YAP1 showed significant downregulation during progressive tendon degeneration and marked upregulation following surgical repair. Histological improvements in collagen organization corresponded with YAP1 re-expression during the recovery phase. YAP1 was consistently reduced in human degenerative tendons. In vitro, mechanical loading enhanced the nuclear localization of YAP1 and upregulated tendon-specific gene expression, confirming its mechanosensitivity. These findings establish YAP1 as a mechanotransducer and a promising biomarker of tendon degeneration and regeneration, with potential therapeutic relevance. This study demonstrated the translational value of YAP1 by integrating animal, human, and in vitro models to identify a robust marker of tendon remodeling.

Restoration of the hip center of rotation (COR) is a primary goal in total hip arthroplasty (THA). Although the teardrop has been widely used as a reference for acetabular cup positioning, its effect on offsets remains uncertain. We conducted a computed tomography–based simulation study of 60 hips (30 osteoarthritis, 30 osteonecrosis of the femoral head) undergoing THA. The contralateral, unaffected hip served as the control. The acetabular cup was positioned just lateral to the teardrop, aligned with the true floor of the acetabulum using preoperative templating software. Acetabular, femoral, and vertical offsets (AO, FO, and VO) were measured bilaterally, and the horizontal and vertical displacements of the COR were evaluated. Compared to the contralateral unaffected side, AO and FO significantly decreased and VO significantly increased on the surgical side (p < 0.01). The COR shifted medially and superiorly in both OA and ONFH groups (average: 2.7–2.8 mm medial, 2.0–2.8 mm superior). In the OA group, global offset (GO), the sum of AO and FO, decreased by 4.7 mm due to a significant reduction in FO. Teardrop-based positioning of the acetabular cup results in medial and superior displacement of the COR, consequently reducing AO and GO. In patients with osteoarthritis, a decreased FO further compromises GO, making femoral component adjustment essential for biomechanical restoration. Further investigation into the clinical ramifications of these offset changes is warranted.

MicroRNAs are small non-coding RNAs that regulate cellular pathways by targeting multiple mRNAs, playing critical roles in skeletal development and homeostasis. Our previous miRNA profiling studies identified higher levels of miR-127-3p in the hypertrophic zone of developing human growth plates while another group found this miRNA to be more highly expressed in murine hindlimb cartilage compared to calvarial bone. Other published work revealed elevated circulating miR-127-3p levels in osteoporotic patients and in long bones of ovariectomized mice. Collectively, these findings suggest a role for miR-127-3p in regulating bone formation. To fill a knowledge gap, we designed a study to determine the function of miR-127-3p in regulating osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSCs). While inhibition of miR-127-3p had no effect, mimic overexpression robustly inhibited in vitro osteogenesis. Bulk RNA-sequencing showed a number of cellular pathways affected, including suppression of proliferation-related pathways, which was confirmed by decreased BrdU incorporation. To assess the translational potential of the bone suppressing function of this miRNA, we utilized a pre-clinical mouse model of trauma-induced heterotopic ossification involving Achilles tendon transection. Local delivery of miR-127-3p mimics via peptide-based nanoparticle technology significantly reduced ectopic bone formation at the proximal site of the transected tendon. These studies demonstrate that approaches to overexpress miR-127-3p and induce bone suppressing activity may be of therapeutic value as a means to treat many forms of heterotopic ossification.