We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/β-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.

The nail is a continuous skin appendage. Cells located around the nails, which display coordinated homeostatic dynamics and release a flow of stem cells in response to regeneration, have been identified in mice. However, very few studies regarding human nail stem cells exist in the literature. Using specimens isolated from humans, we detected an unreported population of cells within the basal layer of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail root. These cells were multi-expressing and expressed stem cell markers, such as keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very similar to mouse nail stem cells in terms of cell marker expression and their location within the nail. We also found that the putative nail stem cells maintained their abundance with advancing age, but cell proliferation and nail growth rate were decreased on comparison of young and aged specimens. To summarize, we found a putative population of stem cells in postnatal human nails located at NPFs and the nail matrix. These cells may have potential for cell differentiation and be capable of responding to injury, and were retained, but may be hypofunctional during aging.

Objective: To assesse the outcomes of one-stage limb reconstruction after removal of skin cancers defect. Methods: This prospective study was conducted from September 2017 to January 2020 and included 15 patients. All patients underwent extensive tumor resection and one-stage Pelnac^® reconstruction of large skin defects, and regular postoperative follow-up was scheduled. At the 6-month follow-up, tumor recurrence and scar quality was assessed using the Vancouver Scar Scale (VSS). None of the patients exhibited infection, wound necrosis, hematoma, seroma, or recurrence. Results: All the skin grafts were well accepted by the patients. Nine patients reported normal or near-normal sensory function, while six reported slight sensory loss. No cases of significant functional loss were observed. We enrolled 10 men and 5 women with a mean age of 63.9 years (range: 46-78 years). The mean follow-up duration was 20.6 months (range: 12-36 months). The skin tumors were located on the feet (n = 4), forearms (n = 3), and legs (n = 8). The malignant tumors included malignant melanomas (13.3%), basal cell carcinomas (33.3%), and squamous cell carcinomas (53.3%). The mean operative time was 40.7 min. Two patients underwent radiotherapy. The average length of hospital stay was 2.6 days. The mean skin defect area was 33.2 cm² (range: 16.6-51.6 cm²). The patient satisfaction score (regarding the aesthetic appearance of the grafted area) was 79.7/100, and the VSS score was 3.8. Conclusion: Pelnac^® dermal templates facilitate efficient and reliable reconstruction of skin defects after skin cancer resection.