Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice

Shi, Lingfeng; Xu, Xiaoli; Meng, Biying; He, Kaiyue; Sun, Yin; Tong, Jiayue; Xu, Jinling; Cheng, Yangyang; Gan, Guo-sheng; Xiang, Guangda

doi:10.1007/s00223-021-00897-2

Cited by 8 publications

(14 citation statements)

References 32 publications

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“…Processing of undecalcified bone specimens and cancellous bone histomorphometry was taken as described previously (Shi et al , 2021). Briefly, femora were fixed in 4% paraformaldehyde overnight and then stored in 70% ethanol at 4°C before being processed and embedded in methylmethacrylate.…”

Section: Methodsmentioning

confidence: 99%

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Shi

et al. 2022

EMBO Reports

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Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)-induced bone loss and age-related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCβ-NF-κB and MAPK1/ 3-STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell-derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders.

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Section: Methodsmentioning

confidence: 99%

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Shi

et al. 2022

EMBO Reports

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“…Serum Nrg4 levels were significantly lower in acute coronary syndrome (ACS) and negatively correlated with HDL-C contents, a well-known beneficial lipoprotein, suggesting a possible association of serum Nrg4 levels with ACS prevalence (Rahimzadeh et al, 2020). Nrg4 treatment was revealed to delay the progression of osteoarthritis by exerting anti-inflammatory and anti-apoptotic effects on chondrocytes in vivo and in vitro and alleviating extracellular matrix degradation in vitro (Shi et al, 2022). A study identified significantly increased serum Nrg4 levels in patients with hyperthyroidism and reduced levels after recovery of thyroid function (Li et al, 2019).…”

Section: Nrg4 and Other Metabolic Disordersmentioning

confidence: 99%

“…Nrg4 treatment was revealed to delay the progression of osteoarthritis by exerting anti-inflammatory and anti-apoptotic effects on chondrocytes in vivo and in vitro and alleviating extracellular matrix degradation in vitro ( Shi et al, 2022 ). A study identified significantly increased serum Nrg4 levels in patients with hyperthyroidism and reduced levels after recovery of thyroid function ( Li et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Neuregulin 4 as a novel adipokine in energy metabolism

Liu

Chen

2023

Front. Physiol.

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Adipose tissue has been shown to play a key role in energy metabolism and it has been shown to regulate metabolic homeostasis through the secretion of adipokines. Neuregulin 4 (Nrg4), a novel adipokine secreted mainly by brown adipose tissue (BAT), has recently been characterized as having an important effect on the regulation of energy homeostasis and glucolipid metabolism. Nrg4 can modulate BAT-related thermogenesis by increasing sympathetic innervation of adipose tissue and therefore has potential metabolic benefits. Nrg4 improves metabolic dysregulation in various metabolic diseases such as insulin resistance, obesity, non-alcoholic fatty liver disease, and diabetes through several mechanisms such as anti-inflammation, autophagy regulation, pro-angiogenesis, and lipid metabolism normalization. However, inconsistent findings are found regarding the effects of Nrg4 on metabolic diseases in clinical settings, and this heterogeneity needs to be further clarified by future studies. The potential metabolic protective effect of Nrg4 suggests that it may be a promising endocrine therapeutic target.

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“…Neuregulin 4 (Nrg4), a member of the extracellular ligand family of epidermal growth factor (EGF), is highly expressed in adipose tissue and is involved in cellular communication during tissue development 154,155 . Studies have revealed that the lack of Nrg4 aggravates the apoptosis of chondrocytes, inflammatory response, and the destruction of articular cartilage in OA mice, and the high expression of Nrg4 reverses this pathological process by regulating the MAPK/JNK signaling axis 156 . Similarly, LIM mineralization protein‐1, a member of the LIM domain protein family, is an intracellular non‐secretory protein involved in the regulation of osteoblast differentiation and maturation as well as bone formation, and has also been shown to inhibit chondrocyte apoptosis through the regulation of MAPK/JNK 156 .…”

Section: Apoptosismentioning

confidence: 99%

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

Xiang

Zheng

Liu

et al. 2023

Orthopaedic Surgery

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Osteoarthritis (OA) causes pain and disability in the elderly and has placed a severe burden on healthcare worldwide. Excessive death and decreased density of chondrocytes are recognized as the major pathological characteristic of OA. Chondrocytes have been shown to have multiple forms of death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. The excessive death of chondrocytes often forms a vicious circle with imbalanced chondrocytes extracellular matrix (ECM) metabolism. Therefore, inhibiting chondrocytes excessive death has become a key point that cannot be ignored in the development of OA treatment strategies. We summarized recent studies on the functions and mechanisms of different modes of chondrocyte death and potential therapeutic strategies for OA and offered our views. This may provide direction and theoretical support for formulating OA treatment strategies in the future.

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Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice

Cited by 8 publications

References 32 publications

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Myeloid‐derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation

Neuregulin 4 as a novel adipokine in energy metabolism

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

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