The TRAP activity around OCP granules was much higher than that of HA granules when implanted onto mouse calvaria, while the amount of bone formation around the

granules was much higher for OCP than HA [25]. These results suggest that the degree of osteoclastic resorption of OCP may be associated with the amount of new bone stimulated by OCP [82]. The tissue formation shown in Fig. 2 included reactive bone formation through the creation of the defect, which is usually observed in the medullary site [23] and [46]. The reactive bone formation resulted in enhanced remodeling of bone marrow tissue accompanied by the complete resorption of OCP granules from the medullary site. However, in general, mTOR signaling pathway the OCP granules remained mostly within the repaired cortical bone encapsulated as debris (Fig. 3a and b). This may be one of the characteristics of OCP biodegradation if used in long bone, although the biodegradable properties of OCP through osteoclast-like cellular resorption appear to be the same when implanted into intramembranous bone, such as calvaria bone [25], [81] and [82]. Therefore, OCP is a material that can be remodeled together with bone. It has been reported that body fluids are almost saturated with respect to the OCP phase from studies of calcium phosphate solubilities [84] and the equilibrium

of human serum [85]. X-ray diffraction analysis confirmed that implanted OCP tends to gradually convert to HA over time in various bone sites or subcutaneous sites [19], [30], [75] and [86]. TSA HDAC in vivo Furthermore, Fourier transform infrared spectroscopy (FTIR) verified that the incubation of OCP in medium also facilitates conversion to the HA phase [30]. OCP conversion into the HA phase was accompanied selleck inhibitor by calcium ion consumption into the crystals and inorganic phosphate (Pi) ion release from the crystals [59]. Although the mechanism to promote OCP hydrolysis into HA has not been fully characterized, it is conceivable that physiological fluids include very small amount of fluoride ions [55], which is

a strong ionic promoter of OCP hydrolysis and works at very low concentrations [87], in these physiological conditions. Circulating serum proteins, such as α2HS-glycoproteins, can be adsorbed by OCP in vivo [75]. The advancement of OCP hydrolysis, which has been studied using OCP and its OCP hydrolyzates as adsorbents, modulates the adsorption affinity of bovine serum albumin [48]. Recent proteomic analyses confirmed that OCP can adsorb over one hundred proteins from rat serum [88]. In addition, proteins involved in bone metabolism, such as apoliporoteins, were identified [88], suggesting the possibility that the proteins adsorbed onto OCP influence bone regeneration by OCP in vivo [88], [89], [90] and [91]. When mouse bone marrow stromal ST-2 cells were cultured on culture plates coated with OCP, the OCP significantly stimulated the differentiation of ST-2 cells into osteoblastic cells to a greater extent than HA [30].