The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs’ differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs’ osteogenic differentiation potential by blocking β-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.
3 February 2022 in Journal of Orthopaedic Surgery and Research
Background: The arthroscopic modified Broström procedure, with repair of the anterior talofibular ligament and extensor retinaculum, produces good functional outcomes in patients with chronic lateral ankle instability (CLAI). CLAI can be associated with osteochondral lesions of the talus (OLTs). It remains unclear whether associated limited OLTs affect clinical outcomes in such patients. Methods: This retrospective cohort study included 92 CLAI patients with and without OLTs undergoing an all-inside arthroscopic modified Broström procedure from June 2016 to May 2019. The patients were divided into non-lesion group (n = 32) and lesion group (n = 60) according to whether CLAI was associated or not with OLTs. All the osteochondral lesions less than 15 mm in diameter were managed with bone marrow stimulation techniques (arthroscopic microfracture) at the time of the arthroscopic modified Broström procedure. The Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Function Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports were compared in both groups. Results: Increase in all the functional scores (VAS, AOFAS, KAFS, ATT, and AJPS) in both groups was, respectively, recorded 1 year and 2 years after surgery. At the 1-year and 2-year follow-up, there was no significant difference in the VAS, AOFAS, KAFS, ATT, and AJPS scores between the non-lesion and lesion groups. Conclusion: In patients with CLAI who underwent an arthroscopic modified Broström procedure, the presence of limited OLTs (less than 15 mm in diameter), which required arthroscopic microfracture, did not exert any influence on outcome. Level of Evidence: Level III, a retrospective comparative study.
Background: All-inside arthroscopic procedures are now frequently employed to manage chronic lateral ankle instability (CLAI) with satisfactory functional outcomes. Currently, no evidence-based guidelines exist for all-inside arthroscopic procedures for CLAI. Many surgical decisions remain uncertain and challenging. Sources of data: Published scientific literature in PubMed, MEDLINE, Web of Science, EMBASE, and Cochrane databases. Areas of agreement: All-inside arthroscopic repair and reconstruction procedures are reliable treatments for CLAI. Areas of controversy: The all-inside arthroscopic procedures for CLAI present significant challenges, particularly in the following aspects: Growing points: Given the lack of guidelines for the all-inside arthroscopic procedures for CLAI, this evidence-based clinical practice guideline provides 11 recommendations to address the controversy. Areas timely for developing research: In patients with CLAI undergoing all-inside arthroscopic procedures, comparative studies are urgently needed to establish the optimal timing for weight-bearing, as well as return to work and sports.
Objective: The purpose of this study was to analyze the clinical effect of percutaneous endoscopic medial foraminal discectomy (PEMFD) in the treatment of lumbar disc herniation (LDH).Methods: We retrospectively examined and compared clinical data from 39 single-level LDH patients who underwent PEID and 47 who underwent PEMFD. All the patients were diagnosed with single-level LDH and were treated in Xuzhou Central Hospital for single-segmental lumbar disc herniation between June 2017 and December 2019. Collect and count surgical-related indicators, intraoperative bleeding volume and 24-hour postoperative drainage volume, lower extremity numbness Visual Analogue Scale (VAS), the pain VAS and lumbar Oswestry Disability Index (ODI) scores.Results: Intraoperative bleeding volume and 24-hour postoperative drainage volume were significantly lower in the PEMFD group (p < 0.05). Operation time and length of hospital stay did not significantly differ between the groups. Transient spinal cord injury and surgical site infection did not occur. Recurrence occurred in two patients in each group. Repeat surgery in these patients demonstrated remarkable epidural scarring in the PEID group patients; no scarring was evident in the PEMFD group patients. The numbness VAS score 72 h after surgery and the pain VAS and ODI scores 1 month after surgery significantly differed between groups; however, pain VAS and ODI scores 6, 12, and 24 months after surgery did not. At last follow-up, the modified MacNab criteria outcome did not significantly differ between the groups.Conclusion: PEMFD and PEID have similar short- and medium-term outcomes. However, PEMFD has several advantages: simplicity, lower bleeding volume, and preservation of the LF.
Background: Surgical intervention remains a cornerstone to restore function after acute Achilles tendon rupture (AATR), but evidence-based guidelines for surgical management are limited. Sources of data: A steering committee of 40 orthopedic surgeons identified nine key clinical questions on the surgical management of AATR. A systematic search of PubMed, MEDLINE, Web of Science, Cochrane Library, and EMBASE was conducted for studies published since 1980. Areas of agreement: Surgical management represents a reliable option to manage patients who suffered AATR. A well-designed operative strategy is essential to facilitate early recovery and achieve optimal functional outcomes. Areas of controversy: The surgical management of AATR remains challenging, particularly with respect to defining surgical indications, determining the optimal timing of intervention, selecting the most appropriate patient positioning, choosing between open and minimally invasive techniques, deciding on the role of primary augmentation, and establishing evidence-based postoperative rehabilitation protocols. Growing points: In the absence of established guidelines for the surgical management of AATR, this evidence-based clinical practice guideline provides nine key recommendations designed to address current controversies in the field. Areas timely for developing research: Further studies are warranted to evaluate emerging strategies such as nutraceuticals, biomaterials, cellular therapies, bioprinting, gene therapy, and anti-inflammatory agents, as no single approach has yet been validated as the optimal method to accelerate or enhance recovery following AATR.