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Article

Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk

by
María Crugeiras-Sampedro
1,†,
Lorena Zas-Veiga
1,†,
María Piñeiro-Ramil
1,
Andrés Pazos-Pérez
1,
Verónica López-López
1,
Alberto Jorge-Mora
1,2,
Ana Alonso-Pérez
1,* and
Rodolfo Gómez
1,*
1
Musculoskeletal Pathology Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago University Clinical Hospital, Servizo Galego de Saude (SERGAS), 15706 Santiago de Compostela, Spain
2
Traumatology and Orthopedics Service, A Coruña University Clinical Hospital, Servizo Galego de Saude (SERGAS), 15006 A Coruña, Spain
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(6), 2783; https://doi.org/10.3390/ijms27062783
Submission received: 10 February 2026 / Revised: 3 March 2026 / Accepted: 17 March 2026 / Published: 19 March 2026
(This article belongs to the Special Issue Musculoskeletal Development and Skeletal Pathophysiologies, 3rd Edition)
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Abstract

(1) Heterotopic ossification (HO) is a pathological process characterized by ectopic bone formation in soft tissues, often following trauma or neurological injury, and is associated with spasticity and chronic inflammation. Mesenchymal stem cells (MSCs) play a central role in HO by differentiating into osteoblasts through endochondral or intramembranous ossification, while alternative fates such as adipogenesis are suppressed. In this study, we investigated the effects of two commonly used antispastic drugs, baclofen and tizanidine, on MSC differentiation under adipogenic and inflammatory conditions in vitro. (2) Mouse C3H10T1/2 MSCs were cultured and induced toward adipogenesis in the presence of baclofen or tizanidine, and inflammatory stimuli (Interleukin-1β or lipopolysaccharides) were applied where indicated. Gene expressions of adipogenic and osteochondrogenic markers were assessed by RT-qPCR, while osteopontin protein levels were quantified by Simple Western. (3) Baclofen treatment significantly inhibited adipogenic gene expression and promoted osteochondrogenic markers and osteopontin protein under basal conditions, whereas tizanidine had minimal effects. Under inflammatory conditions, baclofen partially suppressed adipogenesis but did not strongly induce osteochondrogenesis. (4) These findings indicate that baclofen can directly modulate MSC fate, potentially contributing to HO risk, while tizanidine may offer a safer alternative for spasticity management in patients at risk of ectopic bone formation.
Keywords: heterotopic ossification; spasticity; baclofen; tizanidine; mesenchymal stem cells; adipogenesis; osteochondrogenesis; inflammation; ectopic bone formation and MSC differentiation heterotopic ossification; spasticity; baclofen; tizanidine; mesenchymal stem cells; adipogenesis; osteochondrogenesis; inflammation; ectopic bone formation and MSC differentiation

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MDPI and ACS Style

Crugeiras-Sampedro, M.; Zas-Veiga, L.; Piñeiro-Ramil, M.; Pazos-Pérez, A.; López-López, V.; Jorge-Mora, A.; Alonso-Pérez, A.; Gómez, R. Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk. Int. J. Mol. Sci. 2026, 27, 2783. https://doi.org/10.3390/ijms27062783

AMA Style

Crugeiras-Sampedro M, Zas-Veiga L, Piñeiro-Ramil M, Pazos-Pérez A, López-López V, Jorge-Mora A, Alonso-Pérez A, Gómez R. Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk. International Journal of Molecular Sciences. 2026; 27(6):2783. https://doi.org/10.3390/ijms27062783

Chicago/Turabian Style

Crugeiras-Sampedro, María, Lorena Zas-Veiga, María Piñeiro-Ramil, Andrés Pazos-Pérez, Verónica López-López, Alberto Jorge-Mora, Ana Alonso-Pérez, and Rodolfo Gómez. 2026. "Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk" International Journal of Molecular Sciences 27, no. 6: 2783. https://doi.org/10.3390/ijms27062783

APA Style

Crugeiras-Sampedro, M., Zas-Veiga, L., Piñeiro-Ramil, M., Pazos-Pérez, A., López-López, V., Jorge-Mora, A., Alonso-Pérez, A., & Gómez, R. (2026). Baclofen Promotes Osteochondrogenic Commitment of Mesenchymal Stem Cells: Implications for Heterotopic Ossification Risk. International Journal of Molecular Sciences, 27(6), 2783. https://doi.org/10.3390/ijms27062783

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