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Bone resorption activity of osteoclasts differentiated from BM, PB and CB. (A) FESEM images of the bone slices on d14 were taken with 50 × magnification (representative data from one patient). Pit-like resorption pits are pointed with arrows and trench-like resorption pits with arrowheads. (B) Mean resorption pit areas measured from FESEM images on d14. The data in the graph is pooled from 4 patients per culture type and shown as mean ± SEM.
Source publication
Osteoclasts are multinucleated bone resorbing cells that can be differentiated from human monocytes in vitro. There are few studies comparing osteoclastogenesis of different monocyte sources. We compared monocytes from human bone marrow (BM), peripheral blood (PB), and umbilical cord blood (CB) and their osteoclastogenic potential by culturing them...
Citations
... Monocytes play a pivotal role in maintaining immunological homeostasis and preventing the onset of OP [43]. Monocytes differentiate into multinucleated osteoclasts, thereby regulating osteoclastogenesis in bone metabolism [44]. RXRA, IL17RA, NFKB2, and TP53 are closely linked to osteoclastogenesis. ...
Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.
... Monocytes or tissue-specific macrophages are an important source of osteoclasts in inflammatory and immunological environments. Monocytes in the peripheral blood migrate to specific locations in the bones, where they fuse with one another and become mature multinucleated osteoclasts under specific stimulation (Vuoti et al., 2023). Therefore, it is plausible that numerous perivascular and tissue macrophages near the newly formed bone tissue in BCG were attracted and activated by the high number of red blood cells within the new bone matrix. ...
Aim
To assess the efficacy of heterologous fibrin biopolymer (HFB) in promoting alveolar bone healing after tooth extraction in rats.
Materials and Methods
The upper right incisors of 48 Wistar rats were extracted. Toothless sockets were filled with HFB (HFBG, n = 24) or blood clot (BCG, n = 24). The tooth extraction sites were subjected to micro‐computed tomography (micro‐CT), histological, histomorphometric and immunohistochemical (for Runt‐related transcription factor 2/Runx2 and tartrate‐resistant acid phosphatase/TRAP) analyses on days 0, 7, 14 and 42 after extraction.
Results
Socket volume remained similar between days 0 and 14 (69 ± 5.4 mm ³ ), except in the BCG on day 14, when it was 10% lower ( p = .043). Although the number of Runx2+ osteoblasts was high and similar in both groups (34 × 10 ² cells/mm ² ), the HFBG showed lower inflammatory process and osteoclast activity than BCG at 7 days. On day 14, the number of Runx2+ osteoblasts remained high and similar to the previous period in both groups. However, osteoclast activity increased. This increase was 55% lower in the HFBG than BCG. In the BCG, the presence of an inflammatory process and larger and numerous osteoclasts on day 14 led to resorption of the alveolar bone ridge and newly formed bone. On day 42, numbers of Runx2+ osteoblast and TRAP+ osteoclasts decreased dramatically in both groups. Although the BCG exhibited a more mature cortical bone formation, it exhibited a higher socket reduction (28.3 ± 6.67%) and smaller bone volume (37 ± 5.8 mm ³ ) compared with HFBG (socket reduction of 14.8 ± 7.14% and total bone volume of 46 ± 5.4 mm ³ ).
Conclusions
HFB effectively suppresses osteoclast activity and reduces alveolar bone resorption compared with blood clot, thus preventing three‐dimensional bone loss, particularly during the early healing period. HFB emerges as a promising biopharmaceutical material for enhancing healing processes after tooth extraction.
... Moreover, IL-4 fosters proliferation while inhibiting differentiation in osteoblastic cell lines [36]. These intricate interactions underline the significance of monocytes as a valuable model for studying bone-related diseases [53]. ...
Individual aged with various change in cell and cellular microenvironments and the skeletal system undergoes physiological changes that affect the process of bone fracture healing. These changes are accompanied by alterations in regulating critical genes involved in this healing process. Unfortunately, the elderly are particularly susceptible to hip bone fractures, which pose a significant burden associated with higher morbidity and mortality rates. A notable change in older adults is the increased expression of activation, adhesion, and migration markers in circulating monocytes. However, there is a decrease in the expression of co-inhibitory molecules. Recently, research evidence has shown that the migration of specific monocyte subsets to the site of hip fracture plays a crucial role in bone resorption and remodeling, especially concerning age-related factors. In this review, we summarize the current knowledge about uniqueness characteristics of monocytes, and their potential regulation and moderation to enhance the healing process of hip fractures. This breakthrough could significantly contribute to the comprehension of aging process at a fundamental aging mechanism through this initiative would represent a crucial stride for diagnosing and treating age related hip fracture.
... This is because they have a unique ability to undergo the specialized process known as osteoclastogenesis. Osteoclasts are large, multinucleated cells responsible for bone resorption, which is essential for maintaining bone health, remodelling, and repair [54]. The process of osteoclastogenesis begins with the differentiation of hematopoietic stem cells into monocytes [55]. ...
... These cells are derived from the bone marrow and circulate in the bloodstream. Under specific physiological conditions, such as bone remodelling in response to mechanical stress or injury, certain signalling molecules and cytokines are produced in the bone microenvironment [54,55]. To direct the differentiation of osteoclasts from their precursors, osteoblasts and stromal cells express RANKL in response to many bone-resorbing agents, including vitamin D3 [56]. ...
Simple Summary
OFC (Osteitis Fibrosa Cystica) and Brown Tumours, skeletal lesions commonly found in chronic kidney disease (CKD) patients, are influenced by various risk factors, such as age, sex, medications affecting calcium metabolism, and vitamin D deficiency. The primary cause is secondary hyperparathyroidism, leading to imbalances in calcium and phosphorus levels and osteoclast activation. Other factors, like RAAS hyperactivity and chronic inflammation, may also contribute to their development. The recently described involvement of KRAS mutations turned Brown Tumours from reactive lesions to potentially neoplastic lesions. To manage these conditions, pharmacologic treatments like bisphosphonates, calcimimetics, vitamin D supplementation, and denosumab can help by reducing hyperparathyroidism, restoring calcium levels, and preventing OFC occurrence. Brown Tumours, being rare, lack sufficient understanding regarding their manifestation and treatment. However, considering their impact on CKD patients’ quality of life, it is crucial for nephrologists and medical practitioners working with dialysis patients to be aware of various diagnostic and treatment options.
Abstract
Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin–angiotensin–aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS–MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.
... Minimally invasive surgery allows the bone marrow to enter the cartilage defect and promotes spontaneous repair of the injury site through regulatory factors and nutrients contained in the bone marrow and surrounding tissues. Experiments have shown that bone marrow-derived osteoclasts can efficiently absorb bone, whereas bone marrow and its surrounding tissues carry more cytokines associated with cartilage repair [27]. In another experiment, it was found that bone marrow adipogenic lineage precursors (MALPS) efficiently express Colonystimulating factor 1(CSF1) , a growth factor required for osteoclast progenitors, plays an important role in bone resorption [28]. ...
Knee meniscus injury has a high incidence, which can change the load-bearing structure of the knee joint, causing pain and further cartilage damage and osteoarthritis and other related diseases, and is difficult to prevent and treat effectively. Therefore, how to treat meniscus injury has become one of the hot issues concerned by patients and medical staff in recent years. Compared with simple meniscectomy, tissue engineering meniscectomy has fewer adverse effects and some techniques have achieved satisfactory results. At present, the meniscus tissue engineering treatment method is continuously developing and innovating. In this paper, the promising techniques of collagen scaffold implantation, silk fibroin scaffold implantation, hydrogel implantation and bone marrow stimulation were discussed, we hope to provide the basis for the further development of meniscus repair.
Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are derived from myeloid stem cells, are critical for the bone remodeling by destroying bone. In the present study, we explores the impact of NETs, induced by the inflammatory agent calcium ionophore A23187, on the differentiation and activation of osteoclasts, potentially through suppressing RANK expression. Our results collectively suggested that the inhibition of RANKL-mediated osteoclastogenesis by NETs might lead to the suppression of excessive bone resorption during inflammation.
