Bone Alkaline Phosphatase and Tartrate-Resistant Acid Phosphatase: Potential Co-regulators of Bone Mineralization

Abstract

Phosphorylated osteopontin (OPN) inhibits hydroxyapatite crystal formation and growth, and bone alkaline phosphatase (BALP) promotes extracellular mineralization via the release of inorganic phosphate from the mineralization inhibitor inorganic pyrophosphate (PPi). Tartrate-resistant acid phosphatase (TRAP), produced by osteoclasts, osteoblasts, and osteocytes, exhibits potent phosphatase activity towards OPN; however, its potential capacity as a regulator of mineralization has not previously been addressed. We compared the efficiency of BALP and TRAP towards the endogenous substrates for BALP, i.e., PPi and pyridoxal 5′-phosphate (PLP), and their impact on mineralization in vitro via dephosphorylation of bovine milk OPN. TRAP showed higher phosphatase activity towards phosphorylated OPN and PPi compared to BALP, whereas the activity of TRAP and BALP towards PLP was comparable. Bovine milk OPN could be completely dephosphorylated by TRAP, liberating all its 28 phosphates, whereas BALP dephosphorylated at most 10 phosphates. OPN, dephosphorylated by either BALP or TRAP, showed a partially or completely attenuated phosphorylation-dependent inhibitory capacity, respectively, compared to native OPN on the formation of mineralized nodules. Thus, there are phosphorylations in OPN important for inhibition of mineralization that are removed by TRAP but not by BALP. In conclusion, our data indicate that both BALP and TRAP can alleviate the inhibitory effect of OPN on mineralization, suggesting a potential role for TRAP in skeletal mineralization. Further studies are warranted to explore the possible physiological relevance of TRAP in bone mineralization.

Chronic alcohol consumption changes blood marker profile and bone density in rats with apical periodontitis

“…Moreover, bone remodeling during AP is a defensive reaction to root canal infection, tending to an alveolar bone resorption due to an increase in osteoclastic activity. At the same time, ALP, which is important for mineral formation, tends to diminish due to decreased osteoblastic activity, contributing to the similarity of the results between the groups with and without apical lesions under alcohol administration.…”

Glucagon‐like peptide 2 decreases osteoclasts by stimulating apoptosis dependent on nitric oxide synthase

“…It consistent with some reports, for example, cartilage is composed of specialized cells called chondrocytes that produce a large amount of collagenous extracellular matrix and are closer together creating less intercellular space . And TRAP produced by osteoclasts can alleviate the inhibitory effect of OPN on mineralization, suggesting a potential role for TRAP in skeletal mineralization . Furthermore, human calcitonin (hCt) is a small peptide hormone that exerts its physiological effect on Ca(2 + ) metabolism by means of osteoclast‐mediated bone resorption inhibition …”

Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD

“…The predominant role of BALP during mineralization is the inactivation of inhibitory polyphosphates 52 , most importantly the main autocrine calcification inhibitor PP i 53,54 . ALPs are also speculated to inactivate the calcification inhibitor osteopontin through dephosphorylation 55 and a 2017 study showed that human BALP can suppress the inhibitory effect of osteopontin on in vitro mineralization 56 . In addition, ALPs generate P i , which is the substrate of mineralization, by hydrolysation of organic phosphate esters 57 .…”