| Texto completo | |
| Autor(es): |
Fernandes, Celio J. C.
;
van der Eerden, Bram C. J.
;
Silva, Rodrigo A. Foganholi
;
Fuhler, Gwenny M.
;
Peppelenbosch, Maikel P.
;
Zambuzzi, Willian F.
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH; v. 1873, n. 2, p. 17-pg., 2026-02-01. |
| Resumo | |
We investigated how vascular smooth muscle cells (VSMCs) shape osteolineage fate under mechanosignaling, with emphasis on validating effects in mesenchymal stromal cells (MSCs), a more primitive stage than differentiated osteoblasts. Conditioned media from shear-stressed and non-stressed VSMCs challenged primary human osteoblasts and human MSCs for up to 28 days. Across both cell types, VSMCs robustly promoted osteoblast-to-osteocyte plasticity, evidenced by morphological remodeling and increased expression of osteocyte markers (GP38, SOST, DMP1, miR-23a, FGF23). Notably, non-stressed VSMC-conditioned medium elicited stronger osteocyte-function signatures, including a > 10-fold rise in RANKL transcripts, and these responses were recapitulated in MSCs, demonstrating that VSMC cues instruct osteogenic commitment at an earlier lineage stage and converge on an osteocyte-like phenotype. Mechanistically, small extracellular vesicles (sEVs) emerged as key mediators of VSMC-bone crosstalk: sEV cargo from non-stressed VSMCs displayed higher SOST and DMP1 transcripts, along with phosphor - beta-catenin, phospho-connexin-43, and ATP, suggesting pathways that support osteocyte survival and function. Collectively, our data position VSMCs as pivotal instructors of osteolineage progression - from MSC commitment to osteocyte specification - via sEV-dependent communication, with non-stressed VSMCs exerting the strongest effect, particularly on functional readouts such as RANKL. Further, these findings support VSMC-sEV-inspired, cell-free approaches to modulate osteocytogenesis and regulate bone remodeling, while proposing SOST/DMP1/miR-23a as candidate circulating markers of osteocyte function and treatment response. (AU) | |
| Processo FAPESP: | 16/08888-9 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo |
| Beneficiário: | Célio Junior da Costa Fernandes |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 19/21807-6 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo |
| Beneficiário: | Célio Junior da Costa Fernandes |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |
| Processo FAPESP: | 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo |
| Beneficiário: | Willian Fernando Zambuzzi |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 18/10856-3 - Caracterização completa de exossomos de células endoteliais sob estresse de cisalhamento: uma atenção especial às kinases e mRNA |
| Beneficiário: | Célio Junior da Costa Fernandes |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto |