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These are involved in various aspects of bone physiology depending on the cell type and receptor involved, both in normal and disease states, with extracellular ATP being particularly abundant in the bone microenvironment. The P2X7R subtype has been the subject of in-depth research in bone homeostasis. Different splice isoforms and single nucleotide polymorphisms (SNPs) have been discovered in the\n                    <jats:italic>P2RX7<\/jats:italic>\n                    gene, these have functional implications on the receptor, conferring both gain of function (GOF) and loss of function (LOF), with consequences for bone phenotype, turnover and mass. We examined the full length\n                    <jats:italic>P2RX7A<\/jats:italic>\n                    , truncated\n                    <jats:italic>P2RX7B,<\/jats:italic>\n                    their co-expression and different receptor SNPs. The SNPs included the c.489C\u2009&gt;\u2009T variant (p.His155Tyr) GOF, c.946G\u2009&gt;\u2009A (p.Arg307Gln) LOF and c.1513A\u2009&gt;\u2009C (p.Glu496Ala) LOF. The effect of these isoforms and SNPs on the normal cellular behaviour of the TE85 osteoblastic cell line were measured for intracellular calcium uptake, pore formation, cell proliferation, Alkaline phosphatase (ALP) activity, mineralisation, and changes in osteogenic gene expression. The results demonstrate that transfection of\n                    <jats:italic>P2RX7<\/jats:italic>\n                    isoforms  and SNP variants influenced several important bone processes. Compared to TE85 cells all isoform variants had an increased calcium response with only the co-transfected\n                    <jats:italic>P2RX7AB<\/jats:italic>\n                    having pore formation. This variant also had the highest mineralisation and ALP activity but was the least proliferative. Of the co-transfected SNP variants only the TE85\u2009+\u2009P2RX7B\u2009+\u2009155Y GOF cell line had both pore formation and an increased calcium response. Mineralisation was lower in all SNP cell lines as was ALP activity, however, proliferation was increased. Mechanistically, gene expression arrays showed that Nuclear Factor of Activated T-cells 1 (\n                    <jats:italic>NFATc1<\/jats:italic>\n                    ) increased in the highly proliferative cell variants. Osteogenic genes such as Bone morphogenetic protein 2 (\n                    <jats:italic>BMP2)<\/jats:italic>\n                    ,\n                    <jats:italic>ALP<\/jats:italic>\n                    and collagen type I alpha 1 chain (\n                    <jats:italic>COL1A1<\/jats:italic>\n                    ) were increased in the cell variants that had high mineralisation and ALP activity, and were decreased in the highly proliferative variants, demonstrating multiple bone phenotypes depending on GOF\u00a0or\u00a0LOF. In conclusion, this study extends our knowledge into the role of the P2X7R in maintaining bone homeostasis and provides assessment of\n                    <jats:italic>P2RX7<\/jats:italic>\n                    polymorphisms in osteoblasts. In future this could help to identify associations between specific variants and increased\/reduced bone mineral density or accelerated bone loss\/fracture risk in a number of bone related conditions.\n                  <\/jats:p>","DOI":"10.1007\/s11302-026-10171-5","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:51:52Z","timestamp":1782564712000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of P2RX7 functional SNPs on osteoblast cell phenotype, function and signalling- roles in bone homeostasis and osteogenesis"],"prefix":"10.1007","volume":"22","author":[{"given":"Luke","family":"Tattersall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiguang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lisa","family":"Giuliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Adinolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Gartland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"issue":"2","key":"10171_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1080\/03008207.2017.1290085","volume":"59","author":"X Chen","year":"2018","unstructured":"Chen X, Wang Z, Duan N, Zhu G, Schwarz EM, Xie C (2018) Osteoblast\u2013osteoclast interactions. 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