{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOncomodulin, an EF‐hand calcium‐binding protein also known as β‐parvalbumin, is emerging as a critical regulator of calcium homeostasis in sensory cells. Studies have shown that in the cochlea, it is specifically expressed in outer hair cells (OHCs) where its early postnatal onset and precise subcellular localization to the basolateral membrane and hair bundle are thought to support the intricate regulation of Ca²⁺ necessary for tuning auditory sensitivity. In contrast, in vestibular organs its expression is more diffuse and diminishes with age, suggesting distinct mechanistic roles across inner ear regions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its established function in the inner ear, oncomodulin has been implicated in wider neural mechanisms. Notably, its upregulation in selected neuronal populations has been observed in parvalbumin-deficient contexts, indicating a compensatory response in Ca²⁺ buffering within the brain. Moreover, in peripheral neurons, secreted oncomodulin appears to promote regeneration after injury, as evidenced by its role in driving neurite outgrowth and modulating cytokine expression—such as interleukin-6—in dorsal root ganglia following axotomy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses further reveal that oncomodulin’s unique buffering kinetics are pivotal in shaping intracellular Ca²⁺ transients. In cochlear OHCs and transfected cell models, oncomodulin slows Ca²⁺ influx upon stimulation, thereby lowering freely available Ca²⁺ and influencing the maturation of afferent connectivity. These observations underscore its essential role in modulating spontaneous Ca²⁺ activity during critical developmental windows, a process that underlies the refinement of sensory signaling prior to hearing onset."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dwayne D Simmons, Benton Tong, Angela D Schrader, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncomodulin identifies different hair cell types in the mammalian inner ear."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.22424"}], "href": "https://doi.org/10.1002/cne.22424"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20653034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20653034"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yang Yang, Kaitlin Murtha, Leslie K Climer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/JP284690"}], "href": "https://doi.org/10.1113/JP284690"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37642186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37642186"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "B Csillik, B Schwaller, A Mihaly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroscience (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuroscience.2009.10.048"}], "href": "https://doi.org/10.1016/j.neuroscience.2009.10.048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19874871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19874871"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jon P Niemi, Talia DeFrancesco-Oranburg, Andrew Cox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Conditioning Lesion Response in Dorsal Root Ganglion Neurons Is Inhibited in Oncomodulin Knock-Out Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "eNeuro (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/ENEURO.0477-21.2022"}], "href": "https://doi.org/10.1523/ENEURO.0477-21.2022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35131866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35131866"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kaitlin E Murtha, Yang Yang, Federico Ceriani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Calcium (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ceca.2022.102613"}], "href": "https://doi.org/10.1016/j.ceca.2022.102613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35797824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35797824"}]}]}]}