Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis.

Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but its effects on bone metabolism are not well understood. Here, we report that macrophages in eWAT are a main source of osteopontin, which selectively circulates to the bone marrow and promotes the degradation of the bone matrix by activating osteoclasts, as well as modulating bone marrow-derived macrophages (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow of mice. However, the lactate accumulation induced by osteopontin regulation blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy regeneration by ATP6V0d2 in lysosomes. Both surgical removal of eWAT and local injection of either clodronate liposomes (for depleting macrophages) or osteopontin-neutralizing antibody show comparable amelioration of HFD-induced bone loss in mice. These results provide an avenue for developing therapeutic strategies to mitigate obesity-related bone disorders.

Fibrous dysplasia animal models: A systematic review.

BACKGROUND: Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features. OBJECTIVE: Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD. METHODS: A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis. RESULTS: Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers. LIMITATIONS: None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary. CONCLUSION: The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.

Biodegradable Magnesium-Based Implants in Orthopedics-A General Review and Perspectives.

Biodegradable Mg-based metals may be promising orthopedic implants for treating challenging bone diseases, attributed to their desirable mechanical and osteopromotive properties. This Review summarizes the current status and future research trends for Mg-based orthopedic implants. First, the properties between Mg-based implants and traditional orthopedic implants are compared on the following aspects: in vitro and in vivo degradation mechanisms of Mg-based implants, peri-implant bone responses, the fate of the degradation products, and the cellular and molecular mechanisms underlying the beneficial effects of Mg ions on osteogenesis. Then, the preclinical studies conducted at the low weight bearing sites of animals are introduced. The innovative strategies (for example, via designing Mg-containing hybrid systems) are discussed to address the limitations of Mg-based metals prior to their clinical applications at weight-bearing sites. Finally, the available clinical studies are summarized and the challenges and perspectives of Mg-based orthopedic implants are discussed. Taken together, the progress made on the development of Mg-based implants in basic, translational, and clinical research has laid down a foundation for developing a new era in the treatment of challenging and prevalent bone diseases.

Presence of Bacteria in Spontaneous Achilles Tendon Ruptures.

BACKGROUND: The structural pathology of Achilles tendon (AT) ruptures resembles tendinopathy, but the causes remain unknown. Recently, a number of diseases were found to be attributed to bacterial infections, resulting in low-grade inflammation and progressive matrix disturbance. The authors speculate that spontaneous AT ruptures may also be influenced by the presence of bacteria. HYPOTHESIS: Bacteria are present in ruptured ATs but not in healthy tendons. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with spontaneous AT ruptures and patients undergoing anterior cruciate ligament (ACL) reconstruction were recruited for this study. During AT surgical repair, excised tendinopathic tissue was collected, and healthy tendon samples were obtained as controls from hamstring tendon grafts used in ACL reconstruction. Half of every sample was reserved for DNA extraction and the other half for histology. Polymerase chain reaction (PCR) was conducted using 16S rRNA gene universal primers, and the PCR products were sequenced for the identification of bacterial species. A histological examination was performed to compare tendinopathic changes in the case and control samples. RESULTS: Five of 20 AT rupture samples were positive for the presence of bacterial DNA, while none of the 23 hamstring tendon samples were positive. Sterile operating and experimental conditions and tests on samples, controlling for harvesting and processing procedures, ruled out the chance of postoperative bacterial contamination. The species identified predominantly belonged to the Staphylococcus genus. AT rupture samples exhibited histopathological features characteristic of tendinopathy, and most healthy hamstring tendon samples displayed normal tendon features. There were no apparent differences in histopathology between the bacterial DNA-positive and bacterial DNA-negative AT rupture samples. CONCLUSION: The authors have demonstrated the presence of bacterial DNA in ruptured AT samples. It may suggest the potential involvement of bacteria in spontaneous AT ruptures.

A Systematic Review of Anterior Cruciate Ligament Femoral Footprint Location Evaluated by Quadrant Method for Single-Bundle and Double-Bundle Anatomic Reconstruction.

PURPOSE: To unravel the standard position of anterior cruciate ligament (ACL) femoral origin and deduce practical arthroscopic localization and postsurgical evaluation method. METHODS: Two independent reviewers searched PubMed using the terms ACL, footprint, femur, etc. We included studies published since January 1, 2000, in which the results were measured by Bernard's quadrant method. This method consists of 4 distances, including total diameter of lateral condyle along Blumensaat's line (distance t), maximum intercondylar notch height (distance h), distance from center of footprint to proximal border (distance x), and distance from center of footprint to Blumensaat's line (distance y). The data of included studies were combined to calculate theoretical centers and standard area for both ACL as a whole bundle and as anteromedial (AM) and posterolateral (PL) bundles individually. Finally, we translated the combined data to arthroscopic localization and postsurgical evaluation. RESULTS: A total of 13 studies were included. The theoretical centers of ACL as a whole bundle is 28.4% ± 5.1% (x) of distance t and 35.7% ± 6.9% (y) of distance h, whereas AM bundle is 24.2% ± 4%, 21.6% ± 5.2% (x, y) and PL bundle is 32.8% ± 4.7%, 46.7% ± 4.9% (x, y), respectively. The standard area of ACL footprint is a circle with a center of 27.53%, 35.85% (x, y), and a radius of 4.58%, 9.2% (x, y), respectively. Translation of combined data shows that under arthroscopy, for single-bundle ACL reconstruction, the midpoint of distance from border of proximal to distal articular cartilage is the center of anatomic femoral socket. CONCLUSIONS: Combined data unravel the standard position of ACL femoral origin. It can be used by clinicians to localize anatomic tunnel both in surgery and postsurgical evaluation. For single-bundle ACL reconstruction, the midpoint of lateral femoral condyle corresponds to anatomic socket. LEVEL OF EVIDENCE: Level V, systematic review of anatomic studies.

Critical review on the socio-economic impact of tendinopathy.

There are currently no studies that determine the total burden that tendinopathy places on patients and society. A systematic search was conducted to understand the impact of tendinopathy. It demonstrated that the current prevalence is underestimated, particularly in active populations, such as athletes and workers. Search results demonstrate that due to the high prevalence, impact on patients' daily lives and the economic impact due to work-loss, treatments are significantly higher than currently observed. A well-accepted definition by medical professionals and the public will improve documentation and increase awareness, in order to better tackle the disease burden.