Panx3, a member of the pannexin family of single membrane channel-forming glycoproteins, has diverse functions. It can function as a conduit for ATP at the cell surface and as a calcium leak channel in the endoplasmic reticulum, participating in purinergic signalling. PANX3 is critical in the development and ageing of tissues like bone, cartilage, and skin, and is involved in processes such as cellular differentiation and maintaining tissue homeostasis [4]. Gene knockout mouse models have been valuable for studying its functions.

In skin, global Panx3-knockout (KO) mice show sex-specific differences at different ages. The dorsal skin of KO mice generally has reduced dermal and hypodermal areas. Transcriptomic analysis reveals reduced E-cadherin stabilization, Wnt signalling, and epidermal barrier function, along with increased inflammatory signalling and higher dermatitis incidence in aged KO mice, suggesting PANX3 is crucial for maintaining skin architecture, adhesion, and inflammatory responses during skin ageing [1].

In the intervertebral disc (IVD), Panx3 KO mice display differences in gene expression and altered cellular responses to injury. Loss of Panx3 does not significantly impact age-associated histopathological IVD degeneration, but it affects the response to annulus fibrosus needle puncture, with fewer hypertrophic cells in the injured area and more frequent early nucleus pulposus degeneration in adjacent uninjured IVDs [2]. Also, Panx3-deficient mice show no skeletal phenotype after weaning, suggesting its dispensability for postnatal bone remodeling [3].

In osteosarcoma, miR-431-5p can inhibit tumorigenesis by targeting PANX3 [5]. And deletion of Panx3 in mice makes them resistant to the development of surgically induced osteoarthritis [6].

In conclusion, Panx3 is essential for maintaining tissue architecture, adhesion, and inflammatory responses in the skin, and plays a role in the response of the intervertebral disc to mechanical stress. Gene knockout mouse models have been instrumental in revealing its functions in skin ageing, IVD degeneration, bone remodeling, osteosarcoma, and osteoarthritis, providing insights into potential therapeutic targets for these conditions.