SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells

Li, Jing; Li, Na; Chen, Yunfei; Hui, Shangyi; Fan, Junfen; Ye, Buqing; Fan, Zusen; Zhang, Jianguo; Zhao, Robert Chunhua; Zhuang, Qianyu

doi:10.1038/s41419-019-1949-7

Cited by 20 publications

(18 citation statements)

References 55 publications

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“…55,58,59 Under normal conditions, melatonin via an MT2 response has effects on bone metabolism that can result in increases in bone density and bone mass. Melatonin promotes the proliferation of osteoblasts and differentiation of mesenchymal stem cells into osteoblasts via MT2 receptors 4,[60][61][62] and the MAPK pathway. 4 And Wang W et al denoting the presence of a functional abnormality of the melatonin signaling pathway (MT2) in the growth plate chondrocytes in AIS, which might be associated with the abnormal endochondral ossification in AIS patients.…”

Section: The Mechanism Of Action Of Melatonin In Aismentioning

confidence: 99%

“…Melatonin promotes the proliferation of osteoblasts and differentiation of mesenchymal stem cells into osteoblasts via MT2 receptors 4,[60][61][62] and the MAPK pathway. 4 And Wang W et al denoting the presence of a functional abnormality of the melatonin signaling pathway (MT2) in the growth plate chondrocytes in AIS, which might be associated with the abnormal endochondral ossification in AIS patients. 63 There is evidence of abnormal signaling of the downstream melatonin MT2/PKC pathway that may be related to reduced osteogenic differentiation and bone tissue mineralization.…”

Section: The Mechanism Of Action Of Melatonin In Aismentioning

confidence: 99%

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The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis

Liang

Guo

et al. 2021

The FASEB Journal

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Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity with an incidence of 1%-4%. 1 It is seen more frequently in adolescent females than males, for example, a cohort study from Hong Kong found that during adolescence, the ratios of AIS in girls to boys ranged from 2.7 to 8.4 with increasing spinal curvature. 2 Clinically, it is characterized by three-dimensional spine deformity, and especially by scoliosis in the sagittal plane and rotation in the coronal plane. Although the pathogenesis is still unclear, several factors appear related to AIS occurrence, including genetic, 3 endocrine hormones, 4,5 biomechanics 6 and environmental. 7 The association of endocrine hormones and AIS is of particular research interest. Adolescence is a stage of body growth, when the levels of various hormones that regulate body growth and development are changing quickly. Several studies have reported that adolescents who develop AIS have abnormal levels of multiple hormones, suggesting that hormonal factors may play a role in the occurrence and development of AIS (Table 1). For example, AIS is more common in females, suggesting that AIS may be related to abnormal levels of female sex hormones

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Section: The Mechanism Of Action Of Melatonin In Aismentioning

confidence: 99%

Section: The Mechanism Of Action Of Melatonin In Aismentioning

confidence: 99%

The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis

Liang

Guo

et al. 2021

The FASEB Journal

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“…Studies have revealed that melatonin can boost osteoblast differentiation by upregulating osterix protein stability and expression (14), reduce autophagy in high glucose-cultured osteoblasts, and alleviate diabetes-induced osteoporosis by suppressing the ERK pathway (29). In addition, melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow-derived MSCs by preserving SIRT1-mediated intracellular antioxidation(30), and SPRY4 may be partially responsible for the melatonin-mediated osteogenesis of bone marrow-derived MSCs (31). However, it is generally unknown how melatonin promotes the osteogenic potential of bone marrow-derived MSCs undergoing aging.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Enhances Osteoblastogenesis from Senescent Mesenchymal Stem Cells via MMSET Mediated Chromatin Remodeling

Liu

Xie

Han

et al. 2021

Preprint

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Large numbers of elderly people have aging-associated osteoporosis, but efficient approaches to ameliorate bone loss are limited due to our poor understanding of the underlying mechanisms. In this study, we found that melatonin levels in bone marrow decreased with age, and melatonin primarily enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from elderly donors compared with fetal- or young adult-derived MSCs. Mechanistic studies indicated melatonin treatment alleviated the senescence-related hypermethylation of the MMSET promoter, leading to elevated expression of the histone methyltransferase NSD2, and promoted the histone H3 dimethylation modification at lysine 36 of the osteogenic genes RUNX2 and SP7/OSTERIX as a consequence. MMSET depletion partially abolished the effects of melatonin on osteogenesis in senescent MSCs in vitro. Moreover, melatonin treatment promoted bone formation and alleviated the progression of osteoporosis in a mouse model of aging. Clinically, severity of senile osteoporosis (SOP) in patients was associated with melatonin levels in bone marrow plasma and the MMSET expression in MSCs, and melatonin treatment enhanced osteoblastogenesis from MSCs derived from SOP patients. Our study discovered a previously unreported epigenetic regulatory role for melatonin in alleviating MSC senescence and suggests that melatonin may be a potent agent for preventing aging-associated osteoporosis.

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“…Galectin-3 secretion was significantly higher in DISH-BMSCs than NC-BMSC BMSCs have been reported to secrete a variety of cytokines to regulate osteogenic differentiation. (11)(12)(13) To determine the potential factors involved in the enhanced osteogenic differentiation of DISH-BMSCs, we analyzed cytokine expression in culture supernatants using a human cytokine array kit (Supplemental Fig. S4A).…”

Section: Dish-bmscs Exhibited Stronger Osteogenic Differentiation Abi...mentioning

confidence: 99%

“…(9,10) Moreover, BMSCs also regulate osteogenic differentiation by secreting autocrine and paracrine cytokines. (11)(12)(13) Abnormal osteogenic differentiation of BMSCs has been noted as a key mechanism for ectopic ossification in ankylosing spondylitis (AS). (12)(13)(14) Xie and colleagues (12) reported that an imbalance between BMP-2 and Noggin secretion by BMSCs could induce abnormal osteogenic differentiation and accelerated the progression of hyperostosis in AS.…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 Enhances Osteogenic Differentiation of Precursor Cells From Patients With Diffuse Idiopathic Skeletal Hyperostosis via Wnt/β-Catenin Signaling

Wang

et al. 2020

Journal of Bone and Mineral Research

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Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory skeletal disease characterized by the progressive ectopic ossification and calcification of ligaments and enthuses. However, specific pathogenesis remains unknown. Bone marrow mesenchymal stem cells (BMSCs) are a major source of osteoblasts and play vital roles in bone metabolism and ectopic osteogenesis. However, it is unclear whether BMSCs are involved in ectopic calcification and ossification in DISH. The current study aimed to explore the osteogenic differentiation abilities of BMSCs from DISH patients (DISH-BMSCs). Our results showed that DISH-BMSCs exhibited stronger osteogenic differentiation abilities than normal control (NC)-BMSCs. Human cytokine array kit analysis showed significantly increased secretion of Galectin-3 in DISH-BMSCs. Furthermore, Galectin-3 downregulation inhibited the increased osteogenic differentiation ability of DISH-BMSCs, whereas exogenous Galectin-3 significantly enhanced the osteogenic differentiation ability of NC-BMSCs. Notably, the increased Galectin-3 in DISH-BMSCs enhanced the expression of β-catenin as well as TCF-4, whereas attenuation of Wnt/β-catenin signaling partially alleviated Galectin-3-induced osteogenic differentiation and activity in DISH-BMSCs. In addition, our results noted that Galectin-3 interacted with β-catenin and enhanced its nuclear accumulation. Further in vivo studies showed that exogenous Galectin-3 enhanced ectopic bone formation in the Achilles tendon in trauma-induced rats by activating Wnt/βcatenin signaling. The current study indicated that enhanced osteogenic differentiation of DISH-BMSCs was mainly attributed to the increased secretion of Galectin-3 by DISH-BMSCs, which enhanced β-catenin expression and its nuclear accumulation. Our study helps illuminate the mechanisms of pathological osteogenesis and sheds light on the possible development of potential therapeutic strategies for DISH treatment.

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SPRY4 is responsible for pathogenesis of adolescent idiopathic scoliosis by contributing to osteogenic differentiation and melatonin response of bone marrow-derived mesenchymal stem cells

Cited by 20 publications

References 55 publications

The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis

The role of endocrine hormones in the pathogenesis of adolescent idiopathic scoliosis

Melatonin Enhances Osteoblastogenesis from Senescent Mesenchymal Stem Cells via MMSET Mediated Chromatin Remodeling

Galectin-3 Enhances Osteogenic Differentiation of Precursor Cells From Patients With Diffuse Idiopathic Skeletal Hyperostosis via Wnt/β-Catenin Signaling

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