Lehmann Lab

​​​Seeing, smelling, tasting, when our hormones are doing their job and our heart is beating – ​ a certain class of receptors takes on important tasks in all these processes: the so-called G-protein-coupled receptors (GPCR). GPCR belong to the family of membrane proteins and play a central role in almost all physiological processes in our body. They bind a large number of different ligands, which leads to a change in the conformation of the receptor protein and thus to the recognition and activation of intracellular binding partners. Due to their widespread expression and diverse modes of action, it is hardly surprising that some GPCRs are also associated with pathophysiological processes in the human body. 

For this reason, GPCRs are the focus of drug discovery, with approximately 1/3 of all approved drugs targeting GPCRs. Adhesion GPCRs form a subset of this class of receptors and are involved in a variety of physiological processes. Accordingly, these receptors are associated with various human diseases, such as developmental disorders, defects in the nervous system, allergies and cancer. In addition to their seven-transmembrane domain, aGPCRs are characterized by their large extracellular N-termini, which can contain multiple adhesion domains. Apart from classic G-protein signaling, aGPCRs can signal only through their N-termini. Several aGPCRs have recently been implicated in mechanosensitive functions, suggesting that mechanical stimulus processing may be a common feature of this receptor family.​


Dr. Juliane Lehmann
E-Mail: juliane.lehmann@medizin.uni-leipzig.de
Phone: +49 341 - 97 22175
Fax: +49 341 - 97 22159​


​The role of adhesion G protein-coupled receptors in bone homeostasis

Our bones are not a rigid structure - even after they have completed their lengthening, they are in a constant process of building up, breaking down and remodeling. Various cell types such as osteoblasts, osteoclasts and osteocytes maintain bone homeostasis. While osteoblasts build bone, osteoclasts resorb bone tissue, both actions being tightly regulated by osteocytes. Many factors contribute to the regulation of their interaction and differentiation, thereby determining the relative rates of bone formation and resorption. The homeostasis of these processes is critical to prevent damage to bone structure and resultant metabolic bone disease. Research on aGPCRs is still in its infancy, but recent advances have highlighted a unique function for these receptors that combines GPCR- and integrin-like functions. There is increasing evidence that this class of receptors is important in bone development, homeostasis and disease. Which aGPCRs are expressed in osteoblasts, osteoclasts and osteocytes and how do they influence the differentiation and function of the individual bone cells? What role does the function of the aGPCR play as a mechanosensor and how does a loss of individual aGPCRs affect bone homeostasis in vivo? With the help of various in vitro and in vivo experiments, we want to get to the bottom of these questions.​


Validation of the repertoire and functional relevance of aGPCRs in osteoblasts osteoclasts and osteocytes

Although several aGPCRs have been implicated in bone disease or dysfunction, it remains unclear which of these receptors are involved in the regulation of bone homeostasis. By analyzing the expression pattern of all aGPCRs during differentiation of osteoblasts, osteoclasts and osteocytes, we have already identified a few promising candidates. With the help of a receptor-specific knockdown and the stimulation of the respective aGPCR with its agonistic peptide, we want to investigate the contribution of individual aGPCRs to the differentiation and function of bone cells and find out which signals are mediated by the respective receptor.

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Phenotypic relevance of GPR133 in differentiation of osteoblasts and osteoclasts using a receptor-deficient mouse model

Initial investigations have already shown that Gpr133-KO mice have reduced bone mass. However, it is still unclear whether this phenotype results from decreased bone formation or increased bone resorption. To get to the bottom of this question, the bones of the animals are examined in more detail. Among other things, the microarchitecture is examined using µCT and its cellular structure is analyzed using histological methods. In addition, various serum parameters are examined.

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Establishment of an in vitro stretching model for osteoblasts and osteocytes to investigate the role of GPR133 as a metabotropic mechanosensor

Mechanical stress has been shown to promote differentiation of osteoblasts while impeding differentiation into adipocytes. The duration and intensity of the mechanical stimulus plays a decisive role and influences the activation or inhibition of various signaling pathways involved in the differentiation process. Even though several aGPCRs have already been identified as potential mechanoreceptors, we initially focus on GPR133. For this purpose, an in vitro stretching model with primary cells has already been developed in our laboratory. With the help of further experiments we want to investigate the relevance of GPR133 as a mechanoreceptor in osteoblasts and osteocytes.​

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  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.


02/2020 – present

Rudolf Schönheimer Institute of Biochemistry, Leipzig University
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

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, rheumatoid arthritis, diabetes, and obesity​​

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​
Johannisallee 30, House J
04103 Leipzig
+49 341 - 97 22150
+49 341 - 97 22159