Panx3, a member of the pannexin family of single membrane channel-forming glycoproteins, has diverse functions. It is involved in regulating cell-cell and cell-matrix adhesion, proliferation and differentiation balance in many cell types of the musculoskeletal system, such as osteoblasts, chondrocytes, and odontoblasts. It functions in purinergic signalling as an ATP release channel and can act as a calcium leak channel in the endoplasmic reticulum [3].

In skin, Panx3-knockout (KO) mice studies showed that PANX3 is absent in newborn skin but up-regulated with age. KO dorsal skin had sex differences at different ages and generally reduced dermal and hypodermal areas. Transcriptomic analysis of KO epidermis revealed reduced E-cadherin stabilization, Wnt signalling, and increased inflammatory signalling, leading to a higher incidence of dermatitis in aged KO mice, indicating its role in maintaining dorsal skin architecture, keratinocyte adhesion, and inflammatory responses during skin aging [1].

In the intervertebral disc (IVD), Panx3 KO mice showed that loss of Panx3 did not significantly impact age-associated histopathological IVD degeneration but was associated with altered gene expression and AF structure post-injury, suggesting its role in mediating adaptive cellular responses to mechanical stress in the IVD [2].

In bone, Panx3-KO mice had more severe skeletal abnormalities, and Panx3 regulates chondrocyte and osteoblast differentiation, as well as osteoprogenitor cell proliferation [4].

In conclusion, Panx3 plays essential roles in the development, aging, and function of multiple tissues including skin, IVD, and bone. Studies using Panx3 KO mouse models have significantly contributed to understanding its functions in these tissues and associated disease conditions such as skin inflammation, IVD degeneration, and skeletal abnormalities.