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Such ability is compromised in elderly individuals resulting in bone disorders such as osteoporosis, also limiting their clinical usage for cell transplantation and bone tissue engineering strategies. In bone marrow niches, adenine and uracil nucleotides are important local regulators of osteogenic differentiation of MSCs. Nucleotides can be released to the extracellular milieu under both physiological and pathological conditions via (1) membrane cell damage, (2) vesicle exocytosis, (3) ATP\u2010binding cassette transporters, and\/or (4) facilitated diffusion through maxi\u2010anion channels, hemichannels or ligand\u2010gated receptor pores. Nucleotides and their derivatives act via adenosine P1 (A\n                      <jats:sub>1<\/jats:sub>\n                      , A\n                      <jats:sub>2A<\/jats:sub>\n                      , A\n                      <jats:sub>2B<\/jats:sub>\n                      , and A\n                      <jats:sub>3<\/jats:sub>\n                      ) and nucleotide\u2010sensitive P2 purinoceptors comprising ionotropic P2X and G\u2010protein\u2010coupled P2Y receptors. Purinoceptors activation is terminated by membrane\u2010bound ecto\u2010nucleotidases and other ecto\u2010phosphatases, which rapidly hydrolyse extracellular nucleotides to their respective nucleoside 5\u2032\u2010di\u2010 and mono\u2010phosphates, nucleosides and free phosphates, or pyrophosphates. Current knowledge suggests that different players of the \u201cpurinome\u201d cascade, namely nucleotide release sites, ecto\u2010nucleotidases and purinoceptors, orchestrate to fine\u2010tuning regulate the activity of MSCs in the bone microenvironment. Increasing studies, using osteoprogenitor cell lines, animal models and, more recently, non\u2010modified MSCs from postmenopausal women, raised the possibility to target chief components of the purinergic signaling pathway to regenerate the ability of aged MSCs to differentiate into functional osteoblasts. This review summarizes the main findings of those studies, prompting for novel therapeutic strategies to control ageing disorders where bone destruction exceeds bone formation, like osteoporosis, rheumatoid arthritis, and fracture mal\u2010union. J. Cell. Physiol. 231: 1852\u20131861, 2016. \u00a9 2016 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.25303","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T16:41:35Z","timestamp":1452530495000},"page":"1852-1861","source":"Crossref","is-referenced-by-count":41,"title":["Mesenchymal Stem Cells Ageing: Targeting the \u201cPurinome\u201d to Promote Osteogenic Differentiation and Bone Repair"],"prefix":"10.1002","volume":"231","author":[{"given":"J.B.","family":"Noronha\u2010Matos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia e Neurobiologia\u2010Center for Drug Discovery and Innovative Medicines (MedInUP) Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar\u2010Universidade do Porto (ICBAS\u2010UP) 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