Journal of Orthopaedic Research®最新文献

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.

We have recently reported an injectable bioactive glue that promotes healing of avascular meniscus tears by controlling the recruitment and differentiation of endogenous synovial mesenchymal stem/progenitor cells. Although our previous studies with bioactive glue have demonstrated the enhanced healing of avascular meniscus tears both ex vivo and in vivo, the functional properties of the healed menisci were still suboptimal compared to native tissues, likely associated with the immaturity of reconstructed tissue matrix. Thus, this study explored a mechanically regulated tissue maturation approach to enhance the functional properties of meniscus healing. To apply the complex physiological loading exerted on menisci, we designed a meniscus-specific bioreactor system for our well-established wedge-shaped meniscus explant injury healing model. A finite element model confirmed that the bioreactor exerts a combinational loading consisting of compression, tension, shear, and hoop forces, as reminiscent of physiological loading. In terms of timings of loading, we found that a delayed onset of dynamic physiological loading, initiated 5 weeks after bioactive glue application, was significantly more effective in maturing tissue integration than early loading onsets. The improved meniscal tissue integration was dependent on the magnitude of femoral compressive loading. In addition, the application of hoop strain with femoral compression significantly improved the maturation of multi-directional collagen fiber orientations, but applying 10% additional shear strain resulted in poor tissue integration. Together, our data suggests that the onset timing, magnitude, and mode of physiological stimulation play essential roles in the matured healing of avascular meniscus tears guided by our bioactive glue.

The prevalence of surgical scientists is decreasing due to rising complexities associated with these careers. This study determines the prevalence and impact of MD PhD training in academic orthopedic surgery. This was a cross-sectional study of faculty with MD PhD training at departments of orthopedic surgery in the United States. A control group of MD-only faculty was generated via propensity matching in a 3:1 ratio based on MD degree, institutional affiliation, academic rank, and subspecialty training. Study outcomes were peer-reviewed publication volume, h-index, National Institutes of Health (NIH) grant funding totals, and obtainment of department leadership positions. Comparisons were made with non-parametric and Chi-squared tests. There were 108 clinical faculty with MD PhD training at departments of orthopedic surgery (108/2775, 3.9%). In aggregate, MD PhD trained faculty had more peer-reviewed publications (55, IQR (114) vs. 42, IQR (94), p = 0.024), citations (1521, IQR (3122) vs. 738, IQR (2168), p < 0.001), and higher h-index values (18.0, IQR (23) vs. 14.0, IQR (19), p = 0.005) than controls. MD PhD faculty were more likely to obtain NIH research funding (27.8% vs. 3.7%, p < 0.001) and had higher NIH grant funding totals than MD faculty ($131,347,304 vs. $41,964,766). There were similar rates of promotion to department chair, service line chief, residency program director, and fellowship program director between the two cohorts (p > 0.05). Surgical scientists with MD PhD training account for a small percentage of clinical faculty at departments of orthopedic surgery, but have outsized scholarly influence as measured by peer-reviewed publication volume and NIH research grant funding totals.