The BMP antagonist CHORDIN as a regulator of osteoclast formation and function: an in vitro study

Abstract

Periodontitis is a multifactorial chronic inflammatory disease of the periodontium characterized by clinical attachment loss, alveolar bone loss, deep probing depths, and gingivitis. In susceptible individuals, the shift from gingivitis to periodontitis represents a stage which the bacterial challenge has overwhelmed the immune system and any tissue repair is unlikely. Although there is a wealth of knowledge regarding the microbiology of periodontitis, there is still a lack of understanding with respect to the factors that govern the transition from gingivitis to periodontitis. Alveolar bone loss is the hallmark of periodontal disease which is mediated by osteoclasts. The signalling networks that in addition to the RANKL/RANK/OPG network regulate the differentiation of osteoclasts are poorly understood. Bone morphogenic proteins (BMPs) are growth factors with a diverse function affecting many tissues throughout the body such as the formation of bone, tooth, cartilage, and many more. In recent years the effect of BMPs on bone resorption has gained considerable attention. Studies show that the same BMPs that induced bone formation via osteoblasts are also responsible for bone resorption via osteoclasts. In support of this, Graf et al. have shown that BMP2 and its antagonists Twisted Gastrulation (TWSG1) and Chordin (CHRD) were expressed at site of alveolar bone resorption in a periodontal injury model. Therefore, we speculate that the expression of BMP2 and its antagonists in close vicinity to resorption sites may affect osteoclast differentiation and function. In this project, we have taken in-vitro approaches to determine how CHRD regulates osteoclastogenesis. We identified that BMP2, CHRD, and TWSG1 are all induced in early differentiating osteoclasts. Osteoclast differentiation from bone marrow cells did not seem to be altered in CHRD-deficient mice. The characterization of the in-vitro role of CHRD on BMP signaling during osteoclastogenesis is significant, as it reinforces the importance of BMP signalling network in bone remodelling. These new results also help to refine our current understanding of the various effects of recombinant BMP2 in alveolar bone regeneration.