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Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single‐cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV‐releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hemorrhage control has been an important issue in spine surgery. The widely used gelatin sponge is limited by its long-time bleeding control and poor hemorrhage control. Therefore, new techniques are needed to control bleeding in spine surgery. OBJECTIVE: To compare the hemostatic effect of fluid gelatin SurgifloTM with absorbable gelatin sponge in single level posterior lumbar fusion surgery. METHODS: Ninety-eight patients consisting of 52 males and 46 females, aged 54.32 years who received treatment between September 2017 and December 2017 in Xijing Hospital of The Fourth Military Medical University were included in this study. All patients underwent single-level lets lumbar fusion. Among them, 48 patients received intraoperative hemostasis with fluid gelatin SurgifloTM and 50 patients received intraoperative hemostasis with conventional gelatin sponge. Intraoperative bleeding volume, postoperative drainage volume, success rate of hemostasis in 3 minutes and changes of hemoglobin levels in perioperative period were compared between the two groups. RESULTS AND CONCLUSIONS: The operation time in the SurgifloTM group was significantly shorter than that in the gelatin sponge group [(105±26) vs. (118±32) min, P < 0.05]. The amount of intraoperative blood loss and total amount of drainage were (156±57) ml and (1 06±42) ml in the Surgiflo n.t group which were significantly lower than those in the gelatin sponge group [(204±62) ml, (148±35) ml, P < 0.05]. The success rate of hemostasis within 3 minutes in the SurgifloTM group was significantly higher than that in the gelatin sponge group (94% vs. 80%, P < 0.05). The change in hemoglobin level during the perioperative period relative to pre-surgery level was significantly higher in the SurgifloTM group was significantly lower than that in the gelatin sponge group [(12.3±3.6) vs. (22.8±4.3) g/L, P < 0.05]. No complications such as anaphylaxis, immune rejection, or delayed hematoma occurred in both groups. These results suggest that fluid gelatin SurgifloTM can significantly reduce intraoperative blood loss and postoperative drainage volume in single-level lumbar fusion surgery and exhibit better hemostatic effects. [ABSTRACT FROM AUTHOR]

Inflammation and angiogenesis, the major pathological changes of osteoarthritis (OA), are closely associated with joint pain; however, pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated. Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint. Microarray-based transcriptome analysis, besides quantitative real-time polymerase chain reaction, was performed to identify differentially expressed genes (DEGs). Overall, 182 DEGs (fold change ≥ 2, P < 0.05) were identified between the control and unilateral anterior crossbite groups: 168 were upregulated and 14 were downregulated. On subjecting significant DEGs to enrichment analyses, inflammation and angiogenesis were identified as the most affected. Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling. Furthermore, angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling. Protein-protein interaction analysis revealed a close interaction between inflammation- and angiogenesis-related DEGs, suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Pi3kcd), cathelicidin antimicrobial peptide (Camp), C-X-C motif chemokine receptor 4 (Cxcr4), and MYB proto-oncogene transcription factor (Myb) play a central role in their interaction. To summarize, our findings reveal that in subchondral bone of osteoarthritic joints, signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain; moreover, our data highlight potential targets for the inhibition of OA pain., Competing Interests: Conflicts of interest statement: The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this work.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR + fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR + fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Calcification of cartilage by hydroxyapatite is a hallmark of osteoarthritis and its deposition strongly correlates with the severity of osteoarthritis. However, no effective strategies are available to date on the prevention of hydroxyapatite deposition within the osteoarthritic cartilage and its role in the pathogenesis of this degenerative condition is still controversial. Therefore, the present work aims at uncovering the pathogenic mechanism of intra-cartilaginous hydroxyapatite in osteoarthritis and developing feasible strategies to counter its detrimental effects. With the use of in vitro and in vivo models of osteoarthritis, hydroxyapatite crystallites deposited in the cartilage are found to be phagocytized by resident chondrocytes and processed by the lysosomes of those cells. This results in lysosomal membrane permeabilization (LMP) and release of cathepsin B (CTSB) into the cytosol. The cytosolic CTSB, in turn, activates NOD-like receptor protein-3 (NLRP3) inflammasomes and subsequently instigates chondrocyte pyroptosis. Inhibition of LMP and CTSB in vivo are effective in managing the progression of osteoarthritis. The present work provides a conceptual therapeutic solution for the prevention of osteoarthritis via alleviation of lysosomal destabilization., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)