Damage associated molecular patterns in necrotic femoral head inhibit osteogenesis and promote fibrogenesis of mesenchymal stem cells

Deng, Zhuo; Ren, Yinshi; Park, Min Sung; Kim, Harry K.W.

doi:10.1016/j.bone.2021.116215

Cited by 15 publications

(12 citation statements)

References 57 publications

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“…The porcine bone marrow‐derived mesenchymal cells (pBMMCs) were isolated from the iliac crest of pigs 28 . Passages 3–5 were used for the osteogenic assays.…”

Section: Methodsmentioning

confidence: 99%

“…The porcine bone marrow-derived mesenchymal cells (pBMMCs) were isolated from the iliac crest of pigs. 28 Passages 3-5 were used for the osteogenic assays. A total of 5 × 10 5 cells were seeded into 12-well plates and cultured with the growth medium (GM; minimum essential medium…”

Section: Osteogenic Assessment Of the Postwash Solutionmentioning

confidence: 99%

“…The culture medium was replaced every 2 days. The cells were harvested after 9 days of culture for qPCR analysis and Alizarin Red staining, 28 respectively. The primers for qPCR were listed in Supporting Information: Table S1.…”

Section: Osteogenic Assessment Of the Postwash Solutionmentioning

confidence: 99%

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Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Andre

Boschetto

Gokani

et al. 2022

Journal Orthopaedic Research

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Avascular necrosis (AVN) involves ischemic cell death of the bone. AVN leaves an abundance of necrotic lipids and debris in the bone marrow, which instigates inflammatory bone repair. Consequently, the necrotic bone microenvironment stimulates excessive bone resorption, leading to joint deformities and osteoarthritis.Here, we performed a detergent-assisted bone wash using poloxamer 407 (P407) to clean the necrotic bone environment by removing lipids and necrotic debris. The new concept was tested using an established ex vivo AVN model of porcine cadaver humeral heads. The P407 wash was performed using P407 solution and followed with saline via two intraosseous needles. Visual inspection and image analyses of average pixel light intensity showed that the P407 wash produced a better-cleaned bone than the saline wash. Analyses of the collected bone wash solution showed a two-fold increase in triglycerides (101 vs. 53 mmol/head, p = 0.006) and a 10-fold increase in the dry weight of the removed debris (1.34 vs. 0.13 g/head, p = 0.02) with the P407 wash compared to saline. The histological evaluation showed significantly decreased Oil-Red-O (fats) staining in the P407-washed bone compared with the saline-washed bone. The in vitro assays of Alizarin red and qPCR showed the P407 wash neither altered the osteogenic behaviors of porcine bone marrow-derived mesenchymal cells (pBMMCs) nor raised inflammatory responses of porcine bone marrow-derived macrophages (pBMMs). In conclusion, detergent-assisted bone wash using P407 produced a better removal of nonsoluble debris from the bone marrow space than the saline wash without causing changes to osteogenesis or inflammatory reactions.avascular necrosis, intraosseous bone wash, poloxamer 407 | INTRODUCTIONAvascular necrosis (AVN) is the death of bone, commonly affecting the hip, shoulder, and knee joints. [1][2][3] The annual incidence of hip AVN in the United States is about 10,000-20,000 per year, 4 and over 20 million people in the world will suffer from AVN in the next 10 years. 5 Without treatment, over 50% of the affected joints will develop severe disabling osteoarthritis, 2,6,7 which significantly reduces the quality of life. Total joint replacement (TJR) is often required due to AVN progression, but TJR is a suboptimal treatment

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“…The porcine bone marrow‐derived mesenchymal cells (pBMMCs) were isolated from the iliac crest of pigs 28 . Passages 3–5 were used for the osteogenic assays.…”

Section: Methodsmentioning

confidence: 99%

Section: Osteogenic Assessment Of the Postwash Solutionmentioning

confidence: 99%

See 1 more Smart Citation

Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Andre

Boschetto

Gokani

et al. 2022

Journal Orthopaedic Research

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“…Damage to the osteogenic differentiation of BMMSCs and osteoblast is one of the cytological causes of ONFH 17 . We wanted to investigate whether CST exerted a protective effect of Dex by protecting the osteogenic differentiation capacity.…”

Section: Cst Inhibited Dysfunction Of Osteoblasts Induced By Dexmentioning

confidence: 99%

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

Yuan

You

et al. 2022

Preprint

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Long-term use of glucocorticoids (GCs) is known to be a predominant cause of osteonecrosis of the femoral head (ONFH). Moreover, GCs can mediate apoptosis of various cell types by exaggerating oxidative stress. Previous studies have reported that the AKT pathway might be closely associated with apoptosis and metabolism of osteoblasts in ONFH mediated by GCs. We have previously found that cortistatin (CST) antagonizes oxidative stress and improves cell metabolism as well as apoptosis in several conditions. In this study, we detected that local and systemic CST expression levels were diminished in patients with ONFH compared with femoral neck fracture (FNF). In addition, a GC-induced rat ONFH model was established, which impaired bone quality and angiogenesis and improved osteoblastogenesis in the femoral head. Then, administration of CST attenuated these ONFH phenotypes in this model. Furthermore, osteoblast and endothelial cell lines were cultured and stimulated with dexamethasone (Dex) in the presence or absence of recombinant CST. As a result, Dex induced apoptosis and impaired anabolic metabolism of osteoblasts and suppressed tube formation as well as migration in endothelial cells, while additional treatment with CST reversed this damage to the cells. Moreover, blocking GHSR1a, a well-accepted receptor of CST, or blocking the AKT signaling pathway largely abolished the protective function of CST in Dex-induced disorder of the cells. Taken together, our results indicate that CST has the capability to prevent GC-induced apoptosis and metabolic disorder of osteoblasts in the pathogenesis of ONFH via the GHSR1a/AKT signaling pathway.

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“…ON induces acute cell death that triggers inflammatory cytokine and damage associated molecular patterns (DAMPs) release, skewing bone marrow progenitor cells differentiation and inhibiting mineralization in vitro. 16 ON patients are characterized by imbalanced bone remodeling (increased bone resorption and decreased bone formation) and a defect in the revascularization of the necrotic tissue. Obesity has been demonstrated to have a direct effect on bone metabolism.…”

mentioning

confidence: 99%

Obesity impairs revascularization and bone healing in a mouse model of osteonecrosis

Deng,

Aguirre‐Flores,

Kim

et al. 2023

Journal Orthopaedic Research

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Osteonecrosis of the femoral head (ONFH) is a devastating bone disease that is caused by a disruption of blood supply leading to necrotic cell death. Clinically, it was found that obesity has a high prevalence with ONFH. However, it remains unclear how obesity may directly affect tissue regeneration and bone healing in osteonecrosis (ON). The purpose of this study is to investigate the effects of obesity and weight loss (WL) on ON healing. In this study, we induced obesity and WL in an established surgery‐induced ON mouse model via feeding a high‐fat diet (HFD) and altering the diet respectively. All mice received a surgical induction of ON of distal femoral epiphysis at the age of 12 weeks. HFD was switched to normal diet (ND) after ON surgery to induce WL. Mouse body weight was recorded weekly. Mouse body composition was scanned by DEXA (Dual‐energy X‐ray absorptiometry) right after sacrifice at the age of 16 weeks. The distal femoral bone samples were fixed and embedded for histology such as H&E, immunohistochemistry, and TRAP staining. In this study, we found that HFD‐induced obesity impaired revascularization and bone remodeling showing decreased vessel areas and reduced osteoblast and osteoclast numbers. WL could rescue obesity‐induced bone healing defects. Our study is the first to test the direct effects of obesity and WL on ON bone healing. We believe our work may provide new concepts for osteonecrosis treatment in obese patients.

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Damage associated molecular patterns in necrotic femoral head inhibit osteogenesis and promote fibrogenesis of mesenchymal stem cells

Cited by 15 publications

References 57 publications

Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

Obesity impairs revascularization and bone healing in a mouse model of osteonecrosis

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