The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation

Suwimon Boonrungsiman, Eileen Gentleman, Raffaella Carzaniga, Nicholas D. Evans, David W. McComb, Alexandra E. Porter, Molly M. Stevens

Research output: Contribution to journalArticlepeer-review

346 Citations (Scopus)
300 Downloads (Pure)


Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a sample-preparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization.

Original languageEnglish
Pages (from-to)14170-14175
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
Early online date9 Aug 2012
Publication statusPublished - 28 Aug 2012


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