PT  - JOURNAL ARTICLE
AU  - Melanie Timmen
AU  - Heriburg Hidding
AU  - Martin Götte
AU  - Thaqif El Khassawna
AU  - Daniel Kronenberg
AU  - Richard Stange
TI  - The Heparan Sulfate Proteoglycan Syndecan-1 Influences Local Bone Cell Communication via the RANKL/OPG Axis
AID  - 10.1101/852590
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 852590
4099  - http://biorxiv.org/content/early/2019/11/22/852590.short
4100  - http://biorxiv.org/content/early/2019/11/22/852590.full
AB  - The cell surface heparan sulfate proteoglycan Syndecan-1 acts as a mediator of signals between the extracellular matrix and cells with high significance during pathogenesis. Besides binding a wide variety of molecules (e.g. growth factors, cytokines, matrix molecules) that play a role in essential cellular processes, Syndecan-1 is able to interact with OPG, one of the major regulators of osteoclastogenesis. Therefore, we investigated the influence of endogenous Syndecan-1 in murine osteoblastic and osteoclastic cells during local bone-cell-communication via the RANKL/OPG axis in vitro and the impact of Syndecan-1 deficiency on bone development and aging in an in vivo mouse model.During aging, serum concentration of Syndecan-1 increased in wild type mice. On bone surfaces, expression of RANKL in osteocytes was more prevalent in aged Syndecan-1 deficient mice leading to higher numbers of osteoclasts. However, bone resorption appeared to be decreased in Syndecan-1 deficient mice. The potential of osteoblasts to induce osteoclastogenesis was characterized by a switch of OPG towards RANKL production and can be induced in osteoblasts by prostaglandin E2 and Vitamin D3. This switch also influenced Syndecan-1 expression on transcriptional and protein level. The lack of Syndecan-1 on osteoblasts in co-cultures of osteoblasts and osteoclast impaired the development of osteoclasts by changing cell-communication via the ratio of OPG and RANKL.Syndecan-1 influences local bone cell communication during physiological bone remodelling. Syndecan-1 deficiency alters the release of OPG and RANKL by osteoblasts and osteocytes, and affects the differentiation of osteoclasts in vitro and in vivo in an age-dependent manner in healthy organisms. Syndecan-1 might therefore be of high impact as a new modulator of bone-cell-communication during bone regeneration or bone diseases where Syndecan-1 expression is known to be even more prevalent.