Arbeitsgruppe Lehmann

 

Dr. Juliane Lehmann
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phone: +49 (0) 341 97 22 175
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Arbeitsgruppe Lehmann

 

Dr. Juliane Lehmann
email: Diese E-Mail-Adresse ist vor Spambots geschützt! Zur Anzeige muss JavaScript eingeschaltet sein!
phone: +49 (0) 341 97 22 175
fax: +49 (0) 341 97 22 159

  

Overview

Regulation of bone formation and remodeling through Adhesion GPCRs

To understand how diseases such as osteoporosis, rheumatoid arthritis, and cancer affect bone
it is necessary to understand the biology and function of healthy bone. Bone is a multifunctional, highly dynamic mineralized connective tissue with approximately 5 to 25% of the bone surface undergoing continuous remodeling1,2. Bone remodeling is crucial for the mechanical integrity, restoration of microfractures and regulation of calcium and phosphate release3. Bone remodeling is characterized by the spatial and temporal coupling of bone formation by osteoblasts and bone resorption by osteoclasts4. Imbalances in bone remodeling can be caused by a variety of factors, including menopause-associated hormonal changes, age-related factors, changes in physical activity, drugs, and diseases. Even though various studies have already shown that GPCRs play an important role in bone development and homeostasis5, there are only a few studies that have dealt with the role of aGPCRs in these processes.

 

 

Fig 1. Bone homeostasis is defined by the balance of bone formation and bone resorption. Therefore, bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCs) need to act in concert under the direction of osteocytes, which lay embedded in the bone matrix. OBs and osteocytes originate from mesenchymal stem cells (MSCs) whereas OCs derive from hematopoietic precursors (HSCs). Many factors contribute to the regulation of their interaction and differentiation, thereby determining the relative rates of bone formation and resorption. Even though there are several indications of an involvement of aGPCRs in bone diseases and dysfunction, their role in bone development and homoeostasis has not been studied so far.

  

  1. Parfitt, A. M. Osteonal and hemiosteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. J. Cell. Biochem. 1994: 55, 273–286.
  2. Raisz, L. G. Local and systemic factors in the pathogenesis of osteoporosis. N. Engl. Med. 1988: 318, 818–828.
  3. Weilbaecher, K. N., Guise, T. A. & McCauley, L. K. Cancer to bone: A fatal attraction. Nat. Rev. Cancer. 2011: vol. 11 411–425.
  4. Rodan, G. A. & Martin, T. J. Role of osteoblasts in hormonal control of bone resorption-A hypothesis. Calcif. Tissue. 1981: Int. vol. 33 349–351.
  5. Luo, J., Sun, P., Siwko, S., Liu, M. & Xiao, J. The role of GPCRs in bone diseases and dysfunctions. Bone Research. 2019) doi:10.1038/s41413-019-0059-6.

Research

Our group aims to unravel the expression and functional impact of the complete aGPCR class in different bone cells (osteoblasts, osteocytes and osteoclasts) using various cell lines and primary murine cells. Furthermore, we will determine the impact of receptor knockdown on osteogenesis and osteoclastogenesis and analyze the effect of receptor activation on their function using different assays. This first comprehensive study of aGPCR in the different bone cell types serves as the basis for further research into this class of receptors with regard to their function in bone homeostasis and disease.

Publications

Peer-reviewed Publications

  1. Lehmann J, Thiele S, Baschant U, Rachner TD, Niehrs C, Hofbauer LC, Rauner M. Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen-deficiency-induced bone loss. iScience. 2021;24(3):102224.
  2. Hildebrandt N*, Colditz J*, Dutra C, Goes P, Salbach-Hirsch J, Thiele S, Hofbauer LC, Rauner M. Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus. Sci Rep 2021;11(1)1920*Shared co-first authorship
  3. Schütt J, Sandoval Bojorquez DI, Avitabile E, Oliveros Mata ES, Milyukov G, Colditz J, Delogu LG, Rauner M, Feldmann A, Koristka S, Middeke JM, Sockel K, Fassbender J, Bachmann M, Bornhäuser M, Cuniberti G, Baraban L. Nanocytometer for smart analysis of peripheral blood and acute myeloid leukemia: a pilot study. Nano Lett. 2020;20(9):6572-6581.
  4. Colditz J*, Picke AK*, Hofbauer LC, Rauner M. Contributions of Dickkopf-1 to Obesity-Induced Bone Loss and Marrow Adiposity. JBMR Plus. 2020 Apr 28;4(6):e10364. *Shared co-first authorship
  5. Colditz J, Thiele S, Baschant U, et al. Osteogenic Dkk1 Mediates Glucocorticoid-Induced but Not Arthritis-Induced Bone Loss. J Bone Miner Res. 2019;34(7):1314‐1323.
  6. Tsourdi E*, Colditz J*, Lademann F, Rijntjes E, Köhrle J, Niehrs C, Hofbauer LC, Rauner M. The Role of Dickkopf-1 in Thyroid Hormone-Induced Changes of Bone Remodeling in Male Mice. Endocrinology. 2019;160(3):664‐674. doi:10.1210/en.2018-00998 *Shared co-first authorship
  7. Colditz J, Thiele S, Baschant U, Niehrs C, Bonewald LF, Hofbauer LC, Rauner M. Postnatal Skeletal Deletion of Dickkopf-1 Increases Bone Formation and Bone Volume in Male and Female Mice, Despite Increased Sclerostin Expression. J Bone Miner Res. 2018;33(9):1698‐1707. 

 

Monographs, teaching and manuals

Rauner M, Jähn K, Hemmatian H, Colditz J, Goettsch C. (2020) Cellular Contributors to Bone Homeostasis. In: Aikawa E., Hutcheson J. (eds) Cardiovascular Calcification and Bone Mineralization. Contemporary Cardiology. Humana, Cham.

CV

 

02/2020 – present

Rudolf-Schönheimer-Institute of Biochemistry, University of Leipzig, Leipzig, Germany 
Postdoctoral Researcher with Prof. Ines Liebscher
Focus: Investigating the (patho)physiological role of single aGPCRs in mouse

 

10/2019 – 01/2020

Additional qualification Life Science Management, Leipzig
Trainee
Focus: Planning and execution of clinical trials (monitoring, CRA), drug safety, quality assurance, drug approval, product and project management, marketing, and sales

 

03/2016 – 09/2019

University Hospital Carl Gustav Carus, Dresden
Department of medicine III, Division of endocrinology, diabetes, and metabolic bone disorders
Research associate (PhD student)
Focus: Investigating the role of Dkk-1 in the pathogenesis of postmenopausal osteoporosis

 

10/2015 – 02/2016

University Hospital Carl Gustav Carus, Dresden
Department of Immunology

Research associate
Focus: Cellular and molecular components of the hematopoietic stem cell niche