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.

Distinct myeloid population phenotypes dependent on TREM2 expression levels shape the pathology of traumatic versus demyelinating CNS disorders.

Triggering receptor expressed on myeloid cell 2 (TREM2) signaling often drives opposing effects in traumatic versus demyelinating CNS disorders. Here, we identify two distinct phenotypes of microglia and infiltrating myeloid populations dependent on TREM2 expression levels at the acute stage and elucidate how they mediate the opposing effects of TREM2 in spinal cord injury (SCI) versus multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High TREM2 levels sustain phagocytic microglia and infiltrating macrophages after SCI. In contrast, moderate TREM2 levels sustain immunomodulatory microglia and infiltrating monocytes in EAE. TREM2-ablated microglia (purine-sensing phenotype in SCI and reduced immunomodulatory phenotype in EAE) drive transient protection at the acute stage of both disorders, whereas reduced phagocytic macrophages and lysosome-activated monocytes lead to contrasting neuroprotective and demyelinating effects in SCI versus EAE, respectively. Our study provides comprehensive insights into the complex roles of TREM2 in myeloid populations across diverse CNS disorders, which has crucial implications in devising TREM2-targeting therapeutics.

Lumbar facet joint osteoarthritis as the underlying reason for persistent low back pain after minimally invasive discectomy.

INTRODUCTION: A post-hoc subgroup analysis of prospective collected data in a randomized controlled trial (RCT) of minimally invasive discectomy was conducted, to find out the possible underlying reasons for patients with persistent low back pain (LBP) following surgery. MATERIALS AND METHODS: Patients who were diagnosed with lumbar disc herniation (LDH) and underwent either percutaneous transforaminal endoscopic discectomy or microendoscopic discectomy in our RCT were analyzed. Patients with persistent LBP in 2-year follow-up were compared with the non-LBP patients to determine the underlying reasons. Then, the demographic characteristics, clinical outcomes and radiological parameters of patients with preoperative lumbar facet joint osteoarthritis (LFJOA) were assessed and compared with the non-LFJOA subgroup. RESULTS: 18 patients (8.1%) were reported to have persistent LBP in 2-year follow-up. Significantly higher proportion of preoperative LFJOA were found in the persistent LBP subgroup and was considered to be a risk factor using multivariate analysis. The prevalence of LFJOA is strongly associated with older age, female, high BMI and heavy labor in the LDH population. All of the clinical outcomes including ODI, SF36-PF, SF36-BP, EQ-5D, VAS-back and VAS-leg were worse in LFJOA subgroup in 2-year follow-up. LFJOA subgroup was associated with more adjacent segment degeneration and more lateral recess stenosis. CONCLUSIONS: LFJOA is a possible underlying reason for patients with persistent LBP after minimally invasive discectomy. Surgeons should carefully review the preoperative radiological images to find out whether there is LFJOA in the LDH segment, and kindly diminish the expectation of back pain relief for those patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov at November 14, 2013, registration number NCT01997086. ( https://clinicaltrials.gov/ct2/show/NCT01997086 ).

Identification of chondrocyte subpopulations in osteoarthritis using single-cell sequencing analysis.

Osteoarthritis (OA) is the most common joint disease. Previous studies were focused on general functions of chondrocyte population in OA without elucidating the existence of chondrocyte subpopulations. To investigate the heterogeneity of chondrocyte, here we conducted detailed analysis on the single-cell sequencing data of cartilage cells from OA patients. After quality control, unsupervised K-mean clustering identified seven different subpopulations of chondrocytes in OA. Those subpopulations of chondrocytes were nominated based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis: stress-metabolizing chondrocytes (cluster 1), rhythmic chondrocytes (cluster 2), apoptotic chondrocytes (cluster 3), matrix-synthesis-related chondrocytes (cluster 4), developmental chondrocytes (cluster 5), protein-synthesis-related chondrocytes (cluster 6 and 8), and osteogenesis chondrocytes (cluster 7). We further noticed that the stress-metabolizing chondrocytes (cluster 1) were dominant in early stages of cartilage damage with increased metabolic levels inhibiting cartilage tissue degeneration, while the matrix-synthesis-related chondrocytes (cluster 4) were mainly existed in the late stages of cartilage damage which reorganized collagen fibers with type III collagen disrupting the extracellular matrix and further cartilage damages. Besides, we identified genes NFKBIA and TUBB2B as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Our study identifies different chondrocyte subpopulations in OA, and highlights the potential different functions of chondrocyte subpopulations in the early versus late stages of cartilage damage.

Molecular Dynamics Simulation of Spreading of Mixture Droplets on Chemically Heterogeneous Surfaces.

The dynamic spreading process of mixed droplets on chemically heterogeneous surfaces has attracted significant attention owing to its extensive industrial applications. The spreading of mixture droplets on a chemically heterogeneous surface is more complex than that for pure fluid droplets and needs to be understood further. In this study, molecular dynamic simulations were performed to investigate the dynamic spreading process of R32/R1234yf mixture droplets and water/ethanol mixture droplets of radius 4.7-6.5 nm with different compositions, on chemically heterogeneous surfaces. The variation in the relative spreading radius with time was analyzed and compared with the molecular kinetic theory. It was observed that for the R32/R1234yf mixture, the actual component mole fraction did not deviate from the nominal one in the triple contact region, and the dynamic spreading behavior was identical to that for the pure fluids. Meanwhile, the converse was true for the ethanol/water mixture. The molecular kinetic theory could accurately predict the spreading of droplets for R32/R1234yf mixtures when the mixture properties were used. However, this was not feasible for ethanol/water mixtures. It was observed that the local physical properties in the triple contact line (including the mole fraction and the lyophilic and lyophobic area ratio) play key roles in the spreading of the ethanol/water mixture droplets. The prediction of the dynamic spreading of water/ethanol mixture droplets on chemically heterogeneous surfaces can be improved significantly by using local properties to modify the molecular kinetic theory.