Where Ideas Grow

Neuro & Skeletal Circuits

ABOUT

Our main objective is to address the peripheral signalling molecules involved in the neuro-skeletal crosstalk, and to provide therapeutic targets for the treatment of bone loss and joint degenerative diseases.

 

RESEARCH

An important function of the nervous system is to tightly regulate organs and integrate their biology to maintain whole body homeostasis. Several findings emphasized the neuro-skeletal network as a powerful regulator of skeletogenesis and therefore stimulated interest on elucidating the molecular mechanisms essential for this crosstalk.

The research topics addressed in our group are:

  • The role of sensory innervation in the complex orchestration of bone regeneration
    We aim to depict the key mechanisms behind the interplay between sensory innervation, vascularization and osteogenesis, and to identify the paracrine network involved. This will pave the way to the identification of new therapeutic targets for bone regeneration. To reach this goal we employ state-of-the-art microfluidic technologies, tissue engineering and computational algorithms to study the multicellular communication between sensory neurons, endothelial cells and osteoblasts in three-dimensional (3D) microenvironments.
  • The role of the sympathetic nervous system and its neurotransmitters in regulating chronic inflammation in osteoarticular diseases
    Our previous results showed a total uncoupling of local joint inflammation from the sympathetic activity in arthritic patients with sustained chronic inflammation in hip joints. Our goal is to identify the mechanism behind the repletion of sympathetic innervation in arthritic joint as well as the neuro-immune molecules involved in the persistence of chronic inflammation that characterizes this clinical condition.
  • The involvement of the adrenergic signalling in the development of metastatic bone disease in breast cancer
    Our goal is to uncover the involvement of the adrenergic signalling pathway(s) in the development of bone metastases triggered by each breast cancer subtype. For this purpose, a 3D biomodel of bone metastatic niche, to tailor the human in vivo metastatic bone niche, as well as an animal model of bone metastasis are being explored. This will allow us to identify novel therapeutic targets to tackle the progression of metastatic bone disease.

Team

Selected Publications

Conceição F., Sousa D.M., Loessberg-Zahl J., Vollertsen A.R., Neto E., Søe K., Paredes J., Leferink A., Lamghari M.,
A metastasis-on-a-chip approach to explore the sympathetic modulation of breast cancer bone metastasis. Materials Today Bio13:, 2022. [Journal: Article] [CI: 4] [IF: 10,8 (*)]
DOI: 10.1016/j.mtbio.2022.100219 SCOPUS: 85124535475

Neto E., Monteiro A.C., Leite Pereira C., Simões M., Conde J.P., Chu V., Sarmento B., Lamghari M.,
Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition. Advanced Healthcare Materials11(11):, 2022. [Journal: Article] [CI: 1] [IF: 11,1 (*)]
DOI: 10.1002/adhm.202102305 SCOPUS: 85125234828

Conceição F., Sousa D.M., Paredes J., Lamghari M.,
Sympathetic activity in breast cancer and metastasis: partners in crime. Bone Research9(1):, 2021. [Journal: Review] [CI: 13] [IF: 13,4]
DOI: 10.1038/s41413-021-00137-1 SCOPUS: 85100589741

Leitão L., Neto E., Conceição F., Monteiro A., Couto M., Alves C.J., Sousa D.M., Lamghari M.,
Osteoblasts are inherently programmed to repel sensory innervation. Bone Research8(1):, 2020. [Journal: Article] [CI: 9] [IF: 13,6]
DOI: 10.1038/s41413-020-0096-1 SCOPUS: 85084588982

Najmi Z., Kumar A., Scalia A.C., Cochis A., Obradovic B., Grassi F.A., Leigheb M., Lamghari M., Loinaz I., Gracia R., Rimondini L.,
Evaluation of nisin and ll-37 antimicrobial peptides as tool to preserve articular cartilage healing in a septic environment. Frontiers in Bioengineering and Biotechnology8:, 2020. [Journal: Article] [CI: 12] [IF: 5,9]
DOI: 10.3389/fbioe.2020.00561 SCOPUS: 85087105680

Ribeiro-da-Silva M., Vasconcelos D.M., Alencastre I.S., Oliveira M.J., Linhares D., Neves N., Costa G., Henrique R., Lamghari M., Alves C.J.,
Interplay between sympathetic nervous system and inflammation in aseptic loosening of hip joint replacement. Scientific Reports8(1):, 2018. [Journal: Article] [CI: 9] [IF: 4]
DOI: 10.1038/s41598-018-33360-8 SCOPUS: 85055614881

Neto E., Leitão L., Sousa D.M., Alves C.J., Alencastre I.S., Aguiar P., Lamghari M.,
Compartmentalized microfluidic platforms: The unrivaled breakthrough of in vitro tools for neurobiological research. Journal of Neuroscience36(46):11573-11584, 2016. [Journal: Article] [CI: 69] [IF: 6]
DOI: 10.1523/JNEUROSCI.1748-16.2016 SCOPUS: 84996552043

Vasconcelos D.M., Ribeiro-da-Silva M., Mateus A., Alves C.J., Machado G.C., Machado-Santos J., Paramos-de-Carvalho D., Alencastre I.S., Henrique R., Costa G., Barbosa M.A., Lamghari M.,
Immune response and innervation signatures in aseptic hip implant loosening. Journal of Translational Medicine14(1):, 2016. [Journal: Article] [CI: 15] [IF: 3,8]
DOI: 10.1186/s12967-016-0950-5 SCOPUS: 84978912223

Neto E., Alves C.J., Sousa D.M., Alencastre I.S., Lourenço A.H., Leitão L., Ryu H.R., Jeon N.L., Fernandes R., Aguiar P., Almeida R.D., Lamghari M.,
Sensory neurons and osteoblasts: Close partners in a microfluidic platform. Integrative biology : quantitative biosciences from nano to macro6(6):586-595, 2014. [Journal: Article] [CI: 41] [IF: 3,8]
DOI: 10.1039/c4ib00035h SCOPUS: 84901624359

Ongoing Projects

STRESS AND BREAST CANCER METASTASIS TO BONE: the Yin and Yan of the sympathetic adrenergic signaling
Reference: EXPL/BIA-BQM/0255/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 30-JUN-23
Organ-on-a-chip systems are the animal’s best friends
Reference: ART 3RS Grant 2021 - OoC4Pain
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Animal Research Tomorrow
From 01-MAR-22 to 31-AUG-23
A game changer for the treatment of osteoarthritis: a cost effective combined advanced therapy to treat knee osteoarthritis
Reference: HORIZON-HLTH-2021-TOOL-06-02 - RIA - GA 101057778
Proponent: Fundacion CIDETEC
Sponsor: CE - Comissão Europeia
From 01-MAY-22 to 31-OCT-26
A European Training Network to Combat Bone Pain
Reference: H2020-MSCA-ITN-2018 - GA 814244
Proponent: Kobenhavns Universitet
Sponsor: European Comission
From 01-JAN-19 to 31-DEC-22
Precision medicine for muscoloskeletal regeneration, prosthetics and active ageing
Reference: H2020-MSCA-ITN-2019 - GA 860462
Proponent: Universita Degli Studi Del Piemonte Orientale Amedeo Avogadro
Sponsor: European Comission
From 01-JAN-20 to 30-SEP-24
From pathobioLogy to synoviA on chip: driving rheuMatoId arthritis to the precisioN medicine Goal
Reference: H2020-NMBP-TR-IND-2020-twostage - GA 953121
Proponent: Universita Degli Studi Del Piemonte Orientale Amedeo Avogadro
Sponsor: European Comission
From 01-JAN-20 to 31-DEC-24