Abstract
Osteoimmunology highlights the two-way communication between bone and immune cells. T cell protein tyrosine phosphatase (TCPTP), also known as protein-tyrosine phosphatase non-receptor 2 (PTPN2), is an intracellular protein tyrosine phosphatase (PTP) essential in regulating immune responses and bone metabolism via dephosphorylating target proteins. Tcptp knockout in systemic or specific immune cells can seriously damage the immune function, resulting in bone metabolism disorders. This review provided fresh insights into the potential role of TCPTP in osteoimmunology. Overall, the regulation of osteoimmunology by TCPTP is extremely complicated. TCPTP negatively regulates macrophages activation and inflammatory factors secretion to inhibit bone resorption. TCPTP regulates T lymphocytes differentiation and T lymphocytes-related cytokines signaling to maintain bone homeostasis. TCPTP is also expected to regulate bone metabolism by targeting B lymphocytes under certain time and conditions. This review offers a comprehensive update on the roles of TCPTP in osteoimmunology, which can be a promising target for the prevention and treatment of inflammatory bone loss.
Highlights
Inflammatory bone diseases characterized by severe bone loss, such as osteoarthritis, rheumatoid arthritis, and periodontitis, are a manifestation of imbalance between the skeletal and immune systems [1,2,3]
These studies suggest that T cell protein tyrosine phosphatase (TCPTP) may be a potential treatment target against inflammatory bone loss induced by macrophage-related disorders, for example, periodontitis and synovitis (Figure 2A)
Zhang P. et al found that TCPTP alleviated inflammatory responses and bone resorption in periodontal tissues via the Janus activated kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway in human oral keratinocytes and type 2 diabetes mellitus (T2DM) db/db mice [115]
Summary
Inflammatory bone diseases characterized by severe bone loss, such as osteoarthritis, rheumatoid arthritis, and periodontitis, are a manifestation of imbalance between the skeletal and immune systems [1,2,3]. Their interactions, known as osteoimmunology, were firstly proposed by Choi and Aaron in 2000, which highlights the two-way communication between bone and immune cells [4]. The potential effect of TCPTP in the field of osteoimmunology is less explored. We intended to offer a comprehensive update on the known and potential roles of TCPTP in osteoimmunology in this review. Our study will lay a theoretical foundation for further basic researches of TCPTP in the field of osteoimmunology and provide references for treatment strategies of inflammatory bone diseases
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