24,25-Dihydroxyvitamin D3 cooperates with a stable, fluoromethylene LPA receptor agonist to secure human (MG63) osteoblast maturation

Fluorophosphonate-functionalised titanium via a pre-adsorbed alkane phosphonic acid: a novel dual action surface finish for bone regenerative applications

“…The treatment of cells to quantify ALP activity was similar to that described by us recently [5]. To ensure that the ALP activity was only associated for cells attached to Ti and not to the surrounding plastic, the sample discs were transferred to fresh 24 well tray and the monolayers lysed with 0.…”

“…Of particular relevance to bone formation is the discovery that LPA co-operates with active metabolites of vitamin D3 to secure hOB maturation [3][4][5], an event associated with the provision of a mechanically robust, mineralised matrix. The signalling cross-coupling that occurs between LPA and active vitamin D3 metabolites culminates in synergistic increases in alkaline phosphatase (ALP), an enzyme essential for bone matrix calcification [6].…”

“…Herein, we report the facile functionalisation of Ti using octadecylphosphonic acid (ODPA) for the subsequent attachment of (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant LPA analogue [15][16][17], which we have found to be a potent pairing with 1,25D in promoting hOB maturation [5,18]. The alignment/configuration of Ti-tethered ODPA to FHBP is most likely akin to the self-assembly of phospholipids.…”

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3

“…Unless stated otherwise, all the cell culture experiments described above were performed three times and all data were subject to a one-way analysis of variance (ANOVA) to test for statistical significance as we have reported previously [33]. When a p value of < 0.05 was found, a Tukey multiple comparisons post-test was performed between all groups.…”

Human Osteoblast Growth and Maturation in Response to Metformin and the Thienopyridone, A769662

“…Suffice it to say Met, even as high as 10mM, was unable to evoke any increase in total ALP, either alone or in concert with calcitriol, the active metabolite of D3 vital for securing healthy bone tissue formation [30]. On the contrary, Met actually blunted the ability of D3 and an LPA receptor agonist (FHBP) to induce osteoblast maturation, a robust agent pairing in promoting human osteoblast differentiation [31,32].…”