The axis 2 is divided into 2 main sub-axis:
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IMmunometabolism – Adipocytes and Bone microenvironment (IMun-AB)
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Functional regulation of Bone Marrow Adipocytes as a link between metabolic diseases and osteoporosis
Our research team focuses on identifying the metabolic parameters that are perturbed in both ageing and metabolic diseases such as obesity and type 2 diabetes which can regulate the activities of Bone Marrow Adipocytes (BMAds) and osteoblasts. In that context, we mainly characterize the impact of chronic hyperglycaemia on the BMAd production of adipokines, ROS and extracellular matrix in relationship with osteoblast-driven bone formation and bone quality using in vitro models, the ovariectomy mouse model and clinical samples from postmenopausal patients.
Area of expertise
- Phenotype and regulation of several adipocyte types
- Loss of bone formation and bone quality
- Involvement of metabolites (glucose, free fatty acids) and ROS in bone defects
- menopause, obesity and type 2 diabetes related-osteoporosis
Technology Transfer Potential
- Adipocyte isolation from bone marrow and other adipose tissues, in mouse and clinical samples
- Mouse models of ovariectomy, High Fat Diet and metabolic tests
Selected publications
- Entz L, Falgayrac G, Chauveau C, Pasquier G, & Lucas S. The extracellular matrix of human bone marrow adipocytes and glucose concentration differentially alter mineralization quality without impairing osteoblastogenesis. Bone Reports 2022 17 101622. (doi:10.1016/j.bonr.2022.101622)
- Lucas S, Tencerova M, Weid B von der, Andersen TL, Attané C, Behler-Janbeck F, Cawthorn WP, Ivaska KK, Naveiras O, Podgorski I, Reagan MR, & Eerden BCJ van der. Guidelines for Biobanking of Bone Marrow Adipose Tissue and Related Cell Types: Report of the Biobanking Working Group of the International Bone Marrow Adiposity Society. Frontiers in Endocrinology 2021 12 1137. (doi:10.3389/fendo.2021.744527)
- Rharass T & Lucas S. High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production. Frontiers in Endocrinology 2019 10 607. (doi:10.3389/fendo.2019.00607)
- Rharass T & Lucas S. MECHANISMS IN ENDOCRINOLOGY: Bone Marrow Adiposity and bone, a bad romance? European Journal of Endocrinology 2018 . (doi:10.1530/EJE-18-0182)
- Hardouin P, Rharass T, & Lucas S. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue? Frontiers in Endocrinology 2016 7 85. (doi:10.3389/fendo.2016.00085)
Full Bibliography:
ORCID number: 0000-0001-7530-7486
Team-project members:
Dr G. FALGAYRAC (Raman analyses), Dr D. LETERME (experimental surgery), S. DELPLACE (Histology), V. GAUTHIER (animal experiments), F. MIELLOT (X-ray micro-computed tomography), Pr G. PASQUIER (Orthopaedic surgeon), Pr B. CORTET (Rheumatologist).
Past members: Dr T. RHARASS (postdoctoral fellow, 2016-2017), L. ENTZ (PhD student, 2018-2022), A. TONIONE (M2R, 2019), C. LACHERETZ (M1R, 2013), bachelor students.
IMmunometabolism – Adipocytes and Bone microenvironment (IMun-AB)
Our research team focuses on the immunometabolic regulations of the functional interactions between adipose tissues, including Bone Marrow Adipocytes, and bone microenvironment in the context of obesity and type 2 diabetes. We aim to unravel the underlying mechanisms of bone disorders and fragility associated to altered bioenergetic metabolism (obesity/diabetes) and/or chronic kidney disease. In this immunometabolic context, our researches emphasize on the regulation of antimicrobial peptides of the innate immunity, their secretion and functional role in osteogenesis and bone remodeling. These researches also focus on the Oral-Gut-Bone Marrow axis to investigate the local and systemic role of secreted antimicrobial peptides and other gut microbiota metabolites on the regulation of bone microenvironment.
Areas of Expertise:
- Cellular and Murine models
- Adipose Tissues-Bone Relationships
- Antimicrobial Peptides and Immunometabolism – Obesity and Diabetes
- Chronic Kidney Disease and Bone disorders
- Oral Biology and mandibular bone
Technology Transfer Potential
- Identification of new immunometabolic biomarkers and therapeutic targets for osteoporosis
- Mouse models as in vivo tool for preclinical evaluation of new biologics for the treatment of bone disorders related to metabolic alterations
Selected publications of the team
- Coutel X, Delattre J, Marchandise P, Falgayrac G, Béhal H, Kerckhofs G, Penel G, Olejnik C. Mandibular bone is protected against microarchitectural alterations and bone marrow adipose conversion in ovariectomized rats. Bone. 2019;127:343-352. PMID: 31276849.
- Al Rassy N, Bakouny Z, Matta J, Frenn F, Maalouf G, Rizkallah M, Bachour F, Sebaaly A, Hardouin P, Chauveau C, El Hage R. The relationships between bone variables and physical fitness across the BMI spectrum in young adult women. J Bone Miner Metab. 2019;37(3):520-528. PMID: 30191458.
- Yala S, Boustta M, Gallet O, Hindié M, Carreiras F, Benachour H, Sidane D, Khireddine H. New synthesis method of HA/P(D,L)LA composites: study of fibronectin adsorption and their effects in osteoblastic behavior for bone tissue engineering. J Mater Sci Mater Med. 2016;27(9):140. PMID: 27534400.
- Benachour H, Zaiou M, Samara A, Herbeth B, Pfister M, Lambert D, Siest G, Visvikis-Siest S. Association of human cathelicidin (hCAP-18/LL-37) gene expression with cardiovascular disease risk factors. Nutr Metab Cardiovasc Dis. 2009;19(10):720-8. PMID: 19346112.
Team-project members:
Hamanou BENACHOUR (MCU), Xavier COUTEL (MCU-PH), Christophe CHAUVEAU (PR), Damien LETERME (MCU), Amélie PAQUET (PhD student), Déo-Gratias MENSAH (PhD student), Jérôme DELATTRE (IE), Séverine DELPLACE (AI), Véronique GAUTHIER (AI), Flore MIELLOT (Tech), Nicolas BERTHEAUME (Tech).
