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SP7介导的成骨过程中的分子串扰:调控机制与治疗潜力

Molecular crosstalk in SP7-mediated osteogenesis: Regulatory mechanisms and therapeutic potential.

作者信息

Lang Jun, Morya Vivek Kumar, Kwak Mi-Kyung, Park Sin-Hye, Noh Kyu-Cheol

机构信息

Department of Orthopedic Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, South Korea.

School of Medicine, Hallym University, Chuncheon, South Korea.

出版信息

Osteoporos Sarcopenia. 2025 Jun;11(2):31-37. doi: 10.1016/j.afos.2025.04.003. Epub 2025 May 13.


DOI:10.1016/j.afos.2025.04.003
PMID:40677780
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12266214/
Abstract

SP7, also known as Osterix, is a zinc finger-containing transcription factor, plays a crucial role in osteoblast differentiation and bone formation. This review examines the molecular mechanisms underlying SP7's regulatory functions, highlighting its interactions with key signaling pathways such as BMP-SMAD, Wnt/β-catenin, and HIF-1α. SP7 acts downstream of RUNX2 to regulate osteogenic gene expression, including collagen Type I Alpha 1 (COL1A1), alkaline phosphatase (ALP) and osteocalcin (OCN). The review also explores the role of post-translational modifications, such as phosphorylation and ubiquitination, in modulating SP7's stability and activity. Emerging therapeutic strategies targeting SP7, including gene editing, RNA-based approaches, and small-molecule modulators, are discussed as innovative solutions for treating osteoporosis and other skeletal disorders. The potential for future research into SP7's interactions with non-coding RNAs and angiogenesis pathways is emphasized, underscoring its significance in skeletal health and regenerative medicine. This comprehensive overview consolidates current knowledge of SP7's molecular functions, therapeutic potential, and its pivotal role in bone biology.

摘要

SP7,也被称为osterix,是一种含锌指结构的转录因子,在成骨细胞分化和骨形成中起着关键作用。本综述探讨了SP7调控功能的分子机制,重点介绍了其与BMP-SMAD、Wnt/β-连环蛋白和HIF-1α等关键信号通路的相互作用。SP7在RUNX2下游发挥作用,调节成骨基因表达,包括I型胶原蛋白α1(COL1A1)、碱性磷酸酶(ALP)和骨钙素(OCN)。本综述还探讨了翻译后修饰(如磷酸化和泛素化)在调节SP7稳定性和活性方面的作用。讨论了针对SP7的新兴治疗策略,包括基因编辑、基于RNA的方法和小分子调节剂,作为治疗骨质疏松症和其他骨骼疾病的创新解决方案。强调了未来研究SP7与非编码RNA和血管生成途径相互作用的潜力,突显了其在骨骼健康和再生医学中的重要性。这一全面概述整合了目前关于SP7分子功能、治疗潜力及其在骨生物学中关键作用的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4549/12266214/53c7c644b451/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4549/12266214/9d20d6ec309f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4549/12266214/53c7c644b451/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4549/12266214/9d20d6ec309f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4549/12266214/53c7c644b451/gr2.jpg

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本文引用的文献

[1]
Bone metabolism - an underappreciated player.

NPJ Metab Health Dis. 2024-7-1

[2]
Sclerostin as a new target of diabetes-induced osteoporosis.

Front Endocrinol (Lausanne). 2024-12-10

[3]
Engineering bone/cartilage organoids: strategy, progress, and application.

Bone Res. 2024-11-20

[4]
Combined Effects of Cyclic Hypoxic and Mechanical Stimuli on Human Bone Marrow Mesenchymal Stem Cell Differentiation: A New Approach to the Treatment of Bone Loss.

J Clin Med. 2024-9-28

[5]
Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.

Int J Mol Sci. 2024-9-20

[6]
Mechanoresponsive regulation of tissue regeneration during distraction osteogenesis.

FASEB J. 2024-9-30

[7]
Unraveling the multifaceted role of SIRT7 and its therapeutic potential in human diseases.

Int J Biol Macromol. 2024-11

[8]
Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review.

Biomedicines. 2024-7-23

[9]
Regulation of bone homeostasis: signaling pathways and therapeutic targets.

MedComm (2020). 2024-7-24

[10]
Roles of Sp7 in osteoblasts for the proliferation, differentiation, and osteocyte process formation.

J Orthop Translat. 2024-6-24

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