Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation

Author(s)

Abuna, Rodrigo P. F. ^[1] ; Almeida, Luciana O. ^[1] ; Souza, Alann T. P. ^[1] ; Fernandes, Roger R. ^[1] ; Sverzut, Thales F. V. ^[1] ; Rosa, Adalberto L. ^[1] ; Beloti, Marcio M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Bone Res Lab, Sch Dent Ribeirao Preto, Ave Cafe S-N, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 236, n. 5, p. 3906-3917, MAY 2021.
• Web of Science Citations: 2

Abstract

Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl-histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic-based therapies to treat bone diseases. (AU)

• FAPESP's process: 18/17356-6 - Effect of titanium surface with nanotopography on the interaction between osteoblasts and osteoclasts
• Grantee: Márcio Mateus Beloti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/13290-0 - Cell therapy: evaluation of the effect of mesenchymal stem cells to regenerate bone tissue of rats with Osteoporosis, Diabetes Mellitus or Arterial Hypertension
• Grantee: Alann Thaffarell Portilho de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/14171-0 - Role of Wnt Signaling Pathways in the Osteogenic Potential of Titanium Surface with Nanotopography
• Grantee: Márcio Mateus Beloti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/12622-7 - Cell therapy: potential of mesenchymal stem cells, VEGF-A and BMP-9 to regenerate bone tissue
• Grantee: Adalberto Luiz Rosa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/14711-4 - Role of Wnt Signaling Pathways in the Osteogenic Potential of Titanium Surface with Nanotopography
• Grantee: Rodrigo Paolo Flores Abuna
• Support Opportunities: Scholarships in Brazil - Doctorate