Skeletal development and homeostasis in mammals are modulated by finely coordinated processes of migration, proliferation, differentiation, and death of skeletogenic cells originating from the mesoderm and neural crest. Numerous molecular mechanisms are involved in these regulatory processes, one of which is protein posttranslational modifications, particularly protein tyrosine phosphorylation (PYP). PYP occurs mainly through the action of protein tyrosine kinases (PTKs), modifying protein enzymatic activity, changing its cellular localization, and aiding in the assembly or disassembly of protein signaling complexes. Under physiological conditions, PYP is balanced by the coordinated action of PTKs and protein tyrosine phosphatases (PTPs). Dysregulation of PYP can cause genetic, metabolic, developmental, and oncogenic skeletal diseases. Although PYP is a reversible biochemical process, in contrast to PTKs, little is known about how this equilibrium is modulated by PTPs in the skeletal system. Whole-genome sequencing has revealed a large and diverse superfamily of PTP genes (over 100 members) in humans, which can be further divided into cysteine (Cys)-, aspartic acid (Asp)-, and histidine (His)-based PTPs. Here, we review current knowledge about the functions and regulatory mechanisms of 28 PTPs involved in skeletal development and diseases; 27 of them belong to class I and II Cys-based PTPs, and the other is an Asp-based PTP. Recent progress in analyzing animal models that harbor various mutations in these PTPs and future research directions are also discussed. Our literature review indicates that PTPs are as crucial as PTKs in supporting skeletal development and homeostasis.

哺乳动物的骨骼发育和体内平衡受到源自中胚层和神经嵴的成骨细胞的迁移、增殖、分化和死亡的精细协调过程的调节。这些调节过程涉及许多分子机制，其中之一是蛋白质翻译后修饰，特别是蛋白质酪氨酸磷酸化 (PYP)。PYP 主要通过蛋白质酪氨酸激酶 (PTK) 的作用、改变蛋白质酶活性、改变其细胞定位以及帮助蛋白质信号复合物的组装或拆卸而发生。在生理条件下，PYP 通过 PTKs 和蛋白酪氨酸磷酸酶 (PTPs) 的协调作用来平衡。PYP 的失调可导致遗传、代谢、发育和致癌性骨骼疾病。尽管 PYP 是一个可逆的生化过程，但与 PTKs 相比，我们对骨骼系​​统中 PTPs 如何调节这种平衡知之甚少。全基因组测序揭示了人类 PTP 基因（超过 100 个成员）的庞大而多样的超家族，可进一步分为基于半胱氨​​酸 (Cys)-、天冬氨酸 (Asp)- 和组氨酸 (His) 的 PTP。在这里，我们回顾了目前关于 28 个 PTP 参与骨骼发育和疾病的功能和调控机制的知识；其中 27 个属于 I 类和 II 类基于 Cys 的 PTP，另一个是基于 Asp 的 PTP。还讨论了分析在这些 PTP 中具有各种突变的动物模型的最新进展以及未来的研究方向。我们的文献回顾表明 PTP 在支持骨骼发育和体内平衡方面与 PTK 一样重要。