Ion channels involved in inflammation and pain in osteoarthritis and related musculoskeletal disorders.

Osteoarthritis (OA) is a currently incurable, chronic, progressive, and debilitating musculoskeletal (MSK) condition. One of its hallmark symptoms is chronic nociceptive and neuropathic pain, which significantly reduces the quality of life of patients with OA. Although research into the pathomechanisms of OA pain is ongoing and several pain pathways are well understood, the true source of OA pain remains unclear. Ion channels and transporters are key mediators of nociceptive pain. In this narrative review article, we summarize the state-of-the-art in relation to the distribution and function of ion channels in all major synovial joint tissues in the context of pain generation. We provide an update on the ion channels likely involved in mediating peripheral and central nociceptive pathways in the nervous system in OA pain, including voltage-gated sodium and potassium channels, members of the transient receptor potential (TRP) channel family, and purinergic receptor complexes. We focus on ion channels and transporters that have the potential to be candidate drug targets for pain management in patients with OA. We propose that ion channels expressed by the cells of constituent tissues of OA-afflicted synovial joints including cartilage, bone, synovium, ligament, and muscle, should be more thoroughly investigated and targeted in the context of OA pain. Based on key findings from recent basic research articles as well as clinical trials, we propose novel directions for the development of future analgesic therapies to improve the quality of life of patients with OA.

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review.

Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.