Non traumatic osteonecrosis of the femoral head is associated with low bone mass

Gangji, Valérie; Soyfoo, Muhammad Shahnawaz; Heuschling, Audrey; Afzali, Violaine; Moreno‐Reyes, Rodrigo; Rasschaert, Joanne; Gillet, C.; Fils, Jean‐François; Hauzeur, Jean‐Philippe

doi:10.1016/j.bone.2017.11.005

Cited by 38 publications

(26 citation statements)

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“…Osteoporosis (OP) and non-traumatic osteonecrosis (ON) are bone diseases affecting the quality of life. They are associated with low bone mass and increased fracture risk (1, 2). The prevalence of OP and ON is growing (3) and, although both diseases share some common risk factors (i.e., alcohol abuse and glucocorticoid treatment), their etiology is still not well-understood.…”

Section: Introductionmentioning

confidence: 99%

“…It is now established that OP and ON are characterized by a decreased number of bone marrow mesenchymal stromal cells (MSC) and adipocyte accumulation in the bone marrow niche (4–6). Adipocytes release adipokines, cytokines and free fatty acids (FFA) that might influence skeletal cell survival and function and, hence, affect bone remodeling (2, 7–9).…”

Section: Introductionmentioning

confidence: 99%

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Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation

et al. 2019

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In bone diseases such as osteonecrosis and osteoporosis, a shift toward a preferential differentiation of mesenchymal stromal cells (MSC) into adipocytes at the expense of the osteoblastic lineage is described, leading to excessive accumulation of adipocytes in the bone marrow of the patients. The influence of cytokines and adipokines secreted by adipocytes on skeletal health is already well-documented but the impact of free fatty acids release on bone cell biology and viability is an emerging concept. We have previously demonstrated that the saturated fatty acid (SFA) palmitate (Palm) is cytotoxic for human MSC (hMSC) and osteoblasts whereas oleate (Ole), a monounsaturated fatty acid (MUFA), has no toxic effect. Moreover, Ole protects cells against lipotoxicity. Our observations led us to propose that the toxicity of the SFA is not correlated to its intracellular accumulation but could rather be related to the intracellular SFA/MUFA ratio, which finally determines the toxic effect of SFA. Therefore, in the present study, we have investigated the potential protective role of the enzyme stearoyl-CoA 9-desaturase 1 (SCD1) against the deleterious effects of Palm. SCD1 is an enzyme responsible for desaturation of SFA to MUFA; its activation could therefore lead to modifications of the intracellular SFA/MUFA ratio. In the present study, we showed that hMSC express SCD1 and liver X receptors (LXRs), transcription factors regulating SCD1 expression. Human MSC treatment with a LXRs agonist triggered SCD1 expression and drastically reduced Palm-induced cell mortality, caspases 3/7 activation, endoplasmic reticulum stress and inflammation. We also observed that, in the presence of Palm, the LXRs agonist provoked lipid droplets formation, augmented the total cellular neutral lipid content but decreased the SFA/MUFA ratio when compared to Palm treatment alone. Addition of an inhibitor of SCD1 activity abrogated the positive effects of the LXRs agonist, suggesting that SCD1 could play a key role in protecting hMSC against lipotoxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation

et al. 2019

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“…These risk factors could lead to ischemic changes and eventually result in femoral head collapse and secondary arthritis (Chen et al, 2017). In the early stages of ONFH, the injured blood supply leads to local osteonecrosis and osteoclast-mediated bone resorption (Gangji et al, 2018). Then the osteoblast-mediated reparative reaction initiated (Chen, Liu & Cheng, 2018; Seamon et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The expression of chondrogenesis-related and arthritis-related genes in human ONFH cartilage with different Ficat stages

Chen

Zhong

Wang

et al. 2019

PeerJ

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BackgroundIt has been well known that the degeneration of hip articular cartilage with osteonecrosis of the femoral head (ONFH) increases the instability of hip and accelerates the development process of ONFH. A better understanding of the expression of chondrogenesis-related and arthritis-related genes of cartilage along with the progression of ONFH seems to be essential for further insight into the molecular mechanisms of ONFH pathogenesis.MethodsWe analyzed the differentially expressed gene profile () of human hip articular cartilage with ONFH. The functions and pathway enrichments of differentially expressed genes (DEGs) were analyzed via GO and KEGG analysis. The expression of six selected critical chondrogenesis-related and four arthritis-related genes in eight human hip articular cartilage with femoral neck fracture (FNF) and 26 human hip articular cartilage with different stages ONFH (6 cases of Ficat stage II, 10 cases of Ficat stage III and 10 cases of Ficat stage IV) were detected.ResultsA total of 2,174 DEGs, including 1,482 up-regulated and 692 down-regulated ones, were obtained in the ONFH cartilage specimens compared to the control group. The GO and KEGG enrichment analysis indicated that the function of these DEGs mainly enriched in extracellular matrix, angiogenesis, antigen processing and presentation. The results showed a significant stepwise up-expression of chondrogenesis-related genes, including MMP13, ASPN, COL1A1, OGN, COL2A1 and BMP2, along with the progression of ONFH. The arthritis-related genes IL1β, IL6 and TNFα were only found up-expressed in Ficat IV stage which indicated that the arthritis-related molecular changes were not significant in the progression of ONFH before Ficat III stage. However, the arthritis-related gene PTGS2 was significant stepwise up-expression along with the progression of ONFH which makes it to be a sensitive arthritis-related biomarker of ONFH.ConclusionExpression changes of six chondrogenesis-related and four arthritis-related genes were found in hip articular cartilage specimens with different ONFH Ficat stages. These findings are expected to a get a further insight into the molecular mechanisms of ONFH progression.

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“…Because it is essential for hBMSCs to promote healing [28], the osteosynthesis defects partially explain the poor repair of necrotic areas following stem cell implantation. This defect may be a causative agent of femoral head necrosis in these patients [37].…”

Section: Discussionmentioning

confidence: 90%

Correlation between the efficacy of stem cell therapy for osteonecrosis of the femoral head and cell viability

Sun

Liu

et al. 2020

BMC Musculoskelet Disord

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Background: Osteonecrosis of the femoral head (ONFH) is a common disease that greatly affects the quality of life of patients. Repair of the necrotic area is key to successful treatment. Currently, the combination of stem cell transplantation and decompression is used clinically to promote the repair of necrotic areas based on the characteristics of stem cells. However, a considerable number of patients do not achieve a satisfactory outcome in terms of repair of the femoral head necrotic area, and it is very important to determine the reasons for the poor curative effect. The aim of this study was to investigate the correlation between stem cell viability and the repair efficacy of stem cell therapy combined with core decompression for early-stage ONFH.Methods: A total of 30 patients with idiopathic ONFH underwent core decompression combined with autologous stem cell transplantation. The Harris hip score (HHS) and difference in necrosis area before and after surgery were measured. The mean repair ratio was set as the threshold to divide the patients into group A (ratio above the mean) and group B (ratio below the mean). The ultrastructure, proliferative capacity, and multidirectional differentiation ability were compared between the groups.Results: At 9 months after surgery, the HHS and magnetic resonance imaging (MRI) findings improved by varying degrees. Based on the mean repair ratio of (62.2 ± 27.0)%, the threshold for dividing the patients into groups A and B was set to 62.2%. Better repair (group A) was associated with more rapid proliferation and a healthier ultrastructure. The cells in group A showed stronger specific staining signifying osteogenic and chondrogenic differentiation; alkaline phosphatase (ALP) activity, an indicator of osteogenic differentiation, was higher in group A than in group B (OD, 2.39 ± 0.44 and 1.85 ± 0.52; p < 0.05).Conclusions: The quality of implanted stem cells is closely related to treatment efficacy and determines whether the defective self-repair in the necrotic area can be corrected to enhance repair and thus achieve the desired therapeutic outcome.

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Non traumatic osteonecrosis of the femoral head is associated with low bone mass

Cited by 38 publications

References 25 publications

Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation

Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation

The expression of chondrogenesis-related and arthritis-related genes in human ONFH cartilage with different Ficat stages

Correlation between the efficacy of stem cell therapy for osteonecrosis of the femoral head and cell viability

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