Mathematical model capturing physicochemical and biological regulation of bone mineralization
Abstract Bone mineralization is a complex process tightly regulated by both biological factors such as collagen maturation as well as physicochemical factors such as pH. A previous model of biological mineralization captured the biological regulation of bone mineralization dynamics, but not the impa...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-81472-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850064662839689216 |
|---|---|
| author | Hossein Poorhemati Svetlana V. Komarova |
| author_facet | Hossein Poorhemati Svetlana V. Komarova |
| author_sort | Hossein Poorhemati |
| collection | DOAJ |
| description | Abstract Bone mineralization is a complex process tightly regulated by both biological factors such as collagen maturation as well as physicochemical factors such as pH. A previous model of biological mineralization captured the biological regulation of bone mineralization dynamics, but not the impact of bone microenvironment such as ion availabilities which may be altered in hypo or hyperphosphatemia. To build an integrated model of bone mineralization, we utilized two previously developed models which addressed a distinct aspect of bone mineralization. The first model described the processes of the extracellular matrix formation and maturation, inhibitor and nucleator formation and removal and their combined action in regulating bone mineralization. The second model simulated the bone interstitial fluid (BIF) permissive to precipitation of hydroxyapatite and described the physicochemical process of hydroxyapatite precipitation. The resulting bone mineralization model accounts for biological and physicochemical aspects of the process. The integrated model was analyzed for the impact of physicochemical factors (pH, levels of calcium and phosphate) on the mineralization dynamics. Model predictions were compared to experimental findings using two outcomes characterizing mineralization dynamics: mineralization delay that corresponds to histomorphometry measures of osteoid volume or thickness, and mineralization degree that corresponds to bone mineral density distribution. We identified the limitation of the previously developed model in predicting the mineralization delay observed in the situations of hypophosphatemia and hypocalcemia and proposed a model adaptation that predicts these outcomes. The resulting mathematical model can be used for in silico testing of hypotheses regarding the role of different physicochemical, molecular, or cellular factors in causing a specific disruption in mineralization dynamics. |
| format | Article |
| id | doaj-art-77c565bed29343abb76ff61e021f4964 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-77c565bed29343abb76ff61e021f49642025-08-20T02:49:15ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-81472-1Mathematical model capturing physicochemical and biological regulation of bone mineralizationHossein Poorhemati0Svetlana V. Komarova1Biological and Biomedical Engineering, McGill UniversityBiological and Biomedical Engineering, McGill UniversityAbstract Bone mineralization is a complex process tightly regulated by both biological factors such as collagen maturation as well as physicochemical factors such as pH. A previous model of biological mineralization captured the biological regulation of bone mineralization dynamics, but not the impact of bone microenvironment such as ion availabilities which may be altered in hypo or hyperphosphatemia. To build an integrated model of bone mineralization, we utilized two previously developed models which addressed a distinct aspect of bone mineralization. The first model described the processes of the extracellular matrix formation and maturation, inhibitor and nucleator formation and removal and their combined action in regulating bone mineralization. The second model simulated the bone interstitial fluid (BIF) permissive to precipitation of hydroxyapatite and described the physicochemical process of hydroxyapatite precipitation. The resulting bone mineralization model accounts for biological and physicochemical aspects of the process. The integrated model was analyzed for the impact of physicochemical factors (pH, levels of calcium and phosphate) on the mineralization dynamics. Model predictions were compared to experimental findings using two outcomes characterizing mineralization dynamics: mineralization delay that corresponds to histomorphometry measures of osteoid volume or thickness, and mineralization degree that corresponds to bone mineral density distribution. We identified the limitation of the previously developed model in predicting the mineralization delay observed in the situations of hypophosphatemia and hypocalcemia and proposed a model adaptation that predicts these outcomes. The resulting mathematical model can be used for in silico testing of hypotheses regarding the role of different physicochemical, molecular, or cellular factors in causing a specific disruption in mineralization dynamics.https://doi.org/10.1038/s41598-024-81472-1Mathematical modelingBone biomineralizationHydroxyapatiteMineralization inhibitorsPhysicochemical regulation |
| spellingShingle | Hossein Poorhemati Svetlana V. Komarova Mathematical model capturing physicochemical and biological regulation of bone mineralization Scientific Reports Mathematical modeling Bone biomineralization Hydroxyapatite Mineralization inhibitors Physicochemical regulation |
| title | Mathematical model capturing physicochemical and biological regulation of bone mineralization |
| title_full | Mathematical model capturing physicochemical and biological regulation of bone mineralization |
| title_fullStr | Mathematical model capturing physicochemical and biological regulation of bone mineralization |
| title_full_unstemmed | Mathematical model capturing physicochemical and biological regulation of bone mineralization |
| title_short | Mathematical model capturing physicochemical and biological regulation of bone mineralization |
| title_sort | mathematical model capturing physicochemical and biological regulation of bone mineralization |
| topic | Mathematical modeling Bone biomineralization Hydroxyapatite Mineralization inhibitors Physicochemical regulation |
| url | https://doi.org/10.1038/s41598-024-81472-1 |
| work_keys_str_mv | AT hosseinpoorhemati mathematicalmodelcapturingphysicochemicalandbiologicalregulationofbonemineralization AT svetlanavkomarova mathematicalmodelcapturingphysicochemicalandbiologicalregulationofbonemineralization |