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Chondrocytes are usually considered as nonexcitable cells with no spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling. This study proved that chondrocytes can exhibit robust spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling without explicit external stimuli. The intensity of [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks from individual chondrocytes maintain a consistent spatiotemporal pattern, acting as a unique \u201cfingerprint\u201d for each cell. Statistical analysis revealed lognormal distributions of the temporal parameters of [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks, as well as strong linear correlations between their means and\n                    <jats:sc>sds<\/jats:sc>\n                    . Based on these statistical findings, we hypothesized that the spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks may result from an autocatalytic process and that [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    oscillation is controlled by a threshold\u2010regulating mechanism. To test these 2 mechanisms, we established a multistage biophysical model by assuming the spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling of chondrocytes as a combination of deterministic and stochastic processes. The theoretical model successfully explained the lognormal distribution of the temporal parameters and the fingerprint feature of [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks. In addition, by using antagonists for 10 pathways, we revealed that the initiation of spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks in chondrocytes requires the presence of extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and that the PLC\u2010inositol 1,4,5\u2010trisphosphate pathway, which controls the release of calcium from the endoplasmic reticulum, can affect the initiation of spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    peaks in chondrocytes. The purinoceptors and transient receptor potential vanilloid 4 channels on the plasma membrane also play key roles in the spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling of chondrocytes. In contrast, blocking the T\u2010type or L\u2010type voltage\u2010gated calcium channel promoted the spontaneous calcium signaling. This study represents a systematic effort to understand the features and initiation mechanisms of spontaneous [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    signaling in chondrocytes, which are critical for chondrocyte mechanobiology.\u2014Zhou, Y., Lv, M., Li, T., Zhang, T., Duncan, R., Wang, L., Lu, X. L. Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling. FASEB J. 33, 4675\u20134687 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801460r","type":"journal-article","created":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T14:33:57Z","timestamp":1546439637000},"page":"4675-4687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling"],"prefix":"10.1096","volume":"33","author":[{"given":"Yilu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxi","family":"Lv","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics and Computational Biology University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of Delaware  Newark Delaware USA"},{"name":"Department of Engineering Mechanics Dalian University of Technology  Dalian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiange","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Lucas Lu","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering University of Delaware  Newark Delaware USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2009.12.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2009.0221"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20110766"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2016.5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1707863114"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.12.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2009.04.034"},{"key":"e_1_2_9_10_1","first-page":"178","article-title":"Calcium signals and calcium channels in osteoblastic cells","volume":"18","author":"Duncan R. 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