Cartilage tissue from sites of weight bearing in patients with osteoarthritis exhibits a differential phenotype with distinct chondrocytes subests.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease associated with excessive mechanical loading. The aim here was to elucidate whether different subpopulations of chondrocytes exhibit distinct phenotypes in response to variations in loading conditions. Furthermore, we seek to investigate the transcriptional switches and cell crosstalk among these chondrocytes subsets. METHODS: Proteomic analysis was performed on cartilage tissues isolated from weight-bearing and non-weight-bearing regions. Additionally, single-cell RNA sequencing was employed to identify different subsets of chondrocytes. For disease-specific cells, in vitro differentiation induction was performed, and their presence was confirmed in human cartilage tissue sections using immunofluorescence. The molecular mechanisms underlying transcriptional changes in these cells were analysed through whole-transcriptome sequencing. RESULTS: In the weight-bearing regions of OA cartilage tissue, a subpopulation of chondrocytes called OA hypertrophic chondrocytes (OAHCs) expressing the marker genes SLC39A14 and COL10A1 are present. These cells exhibit unique characteristics of active cellular interactions mediated by the TGFß signalling pathway and express OA phenotypes, distinct from hypertrophic chondrocytes in healthy cartilage. OAHCs are mainly distributed in the superficial region of damaged cartilage in human OA tissue, and on TGFß stimulation, exhibit activation of transcriptional expression of iron metabolism-related genes, along with enrichment of associated pathways. CONCLUSION: This study identified and validated the existence of a subset of OAHCs in the weight-bearing area of OA cartilage tissue. Our findings provide a theoretical basis for targeting OAHCs to slow down the progression of OA and facilitate the repair of cartilage injuries.

Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.

Objective: To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis. Methods: A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs). Results: A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11. Conclusion: BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy. Systematic Review Registration: [https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].