Dose-dependent effects of zoledronic acid on the osteogenic differentiation of human bone marrow stem cells (hBMSCs)

Henrique Hadad; Henrique Rinaldi Matheus; Jason Evan Chen; Youssef Jounaidi; Francisley Ávila Souza; Fernando Pozzi Semeghini Guastaldi

doi:10.1016/j.jormas.2023.101479

Dose-dependent effects of zoledronic acid on the osteogenic differentiation of human bone marrow stem cells (hBMSCs)

J Stomatol Oral Maxillofac Surg. 2023 Dec;124(6):101479. doi: 10.1016/j.jormas.2023.101479. Epub 2023 Apr 18.

Authors

Henrique Hadad¹, Henrique Rinaldi Matheus², Jason Evan Chen³, Youssef Jounaidi⁴, Francisley Ávila Souza⁵, Fernando Pozzi Semeghini Guastaldi⁶

Affiliations

¹ Skeletal Biology Research Center, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA; Department of Diagnosis and Surgery, Oral & Maxillofacial Surgery Division, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, 16.015-050, Brazil.
² Skeletal Biology Research Center, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA; Department of Diagnosis and Surgery, Division of Periodontics, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, 16.015-050, Brazil.
³ Skeletal Biology Research Center, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA.
⁴ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
⁵ Department of Diagnosis and Surgery, Oral & Maxillofacial Surgery Division, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, 16.015-050, Brazil.
⁶ Skeletal Biology Research Center, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02114, USA. Electronic address: fguastaldi@mgh.harvard.edu.

PMID: 37080358
DOI: 10.1016/j.jormas.2023.101479

Abstract

Recent studies have shown that bisphosphonates can also impact osteoblasts besides osteoclasts. This study aimed to evaluate the effects of different concentrations of Zoledronic acid (ZA) during the osteogenic differentiation of human Bone Marrow Stem Cells (hBMSCs) in vitro. Thus, osteogenic differentiation of hBMSCs was conducted with different concentrations of Zoledronic Acid (ZA) (0, 0.1, 1.0, and 5.0 μM) for the first 3 days. Cell metabolism was quantified at 1-, 3-, 7-, and 14 days. At 7- and 14-days, the following analyses were performed: 1) mineralization nodule assay, 2) LIVE/DEAD™, 3) cell adhesion and spreading, 4) alkaline phosphatase (ALP) activity, and 5) qPCR analysis for RUNX-2), ALPL, and COL1 A1. Data were analyzed by ANOVA 2-way, followed by Tukey's post hoc test (p < 0.05). Cell metabolism (3-, 7-, and 14-days) (p < 0.001), mineralization (7-, 14-days) (p < 0.001), and ALP activity (14-days) (p < 0.001) were reduced in ZA 5.0 µM when compared to control (no ZA). Also, ZA 5.0 µM downregulated the expression of RUNX2 at 7- and 14-days (p < 0.001). It is possible to conclude that ZA (5.0 µM) can impair hBMSC differentiation into osteoblasts and interferes with its mineralization phase.

Keywords: Human bone marrow stem cells; Medication-related osteonecrosis of the jaw; Osteogenic differentiation; Zoledronic acid.

MeSH terms

Bone Marrow Cells
Cell Differentiation
Diphosphonates* / pharmacology
Humans
Osteogenesis*
Zoledronic Acid / pharmacology

Substances

Zoledronic Acid
Diphosphonates