key: cord-0994021-38gvlwpm authors: Tao, Huaqiang; Bai, Jiaxiang; Zhang, Weicheng; Zheng, Kai; Guan, Pengfei; Ge, Gaoran; Li, Meng; Geng, Dechun title: Bone biology and COVID-19 infection: Is ACE2 a potential influence factor? date: 2020-08-10 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110178 sha: 3f2235c135e98440b5014d98b6e550240e74b517 doc_id: 994021 cord_uid: 38gvlwpm The outbreak of coronavirus disease 2019 (COVID-19) has posed a severe threat to global health management system since it has been detected in the human body. This pandemic was prompted by severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) and rapidly developed into a public emergency with an alarming increase in cases and deaths. The increasing explorations to SARS-CoV-2 infection guide us to consider whether bone lesion is followed by this pathologic process. We especially focus on the underlying pathobiology that SARS-CoV-2 possibly mediated in bone remodeling and analyze the association of bone destruction with ACE2 in COVID-19 incidence, for preferable understanding the pathogenesis and providing necessary clinical management in orthopedics. Coronavirus are pathogens with high diverse RNA virus that cause respiratory and digestive system injury. An in-depth annotation of newly discovered COVID-19 has revealed a serious and extensive damage to human body system. Once starting up the onset of interstitial pneumonia in progression, it will clinically give rise to severe acute respiratory distress syndrome (ARDS) and ulteriorly deteriorated into multiple organ failure (MOF). Similar to SARS-CoV, which makes incursion into body, SARS-CoV-2 spike protein combines to its functional receptor ACE2 and then be activated to release peptides for fusing membrane (1). Thus, the expression of ACE2 is a pivotal entrance for the invasion of SARS-CoV- Considering that coronaviruses arouses pneumonia and upper respiratory tract infection through ACE2 receptors in ATII cells, we also require taking notice of ACE2-dependent effects on bone tissue. Is ACE2 a potential influence factor that regulate bone biology during COVID-19 infection? 3 Evidence has shown that ACE2 locally expresses in human bone marrow-derived stem/progenitor cells (BMSPCs) and manipulates cytokine-sensing to promote skeletal repair (4). ACE2 promotes AngII degradation and synthetizes Ang1-7, which perform functions by way of Mas receptor. In previous study, literatures revealed osteoblasts and osteoclasts express ACE2/Mas and illustrated how the ACE2/Ang-(1-7)/Mas axis can affect bone metabolism. More specifically, the activation of ACE2/Ang-(1-7)/Mas axis restrains bone resorption and exhibits antiinflammatory property (5) . In Abuohashish's work, he verified ACE-2/Ang1-7/Mas worked as a beneficial RAS axis in order to accelerate the osteo-protective effects on postmenopausal animals, suggesting ACE2 is essential in maintaining bone structure (6) . Once ACE2 was targeted by SARS-CoV-2, the block of ACE2 may give occasion to a decreased bone mass and joint inflammation. Similarly, Duan et al. found ACE2 deficiency worsened diabetes-induced bone marrow microenvironment, which was supported by the dysfunction of migratory and proliferation in BMSCs (7). Nozato et al. found the loss of ACE2 in mice exhibit earlier muscle weakness and a smaller muscle fibre size, Ang-(1-7) can reverse muscle weakness and bone volume in a Masdependent manner. As a consequence, COVID-19 may lead to an earlier muscle disorder and anaphase bone loss via targeting ACE2 in bone marrow microenvironment. Although we have not fully grasped the whole features of COVID-19 and its likely host immunological reactions, pathophysiological proof of this pathogen has attracted our attention to bone metabolism. Without doubt, the deterioration of underlying diseases caused by SARS-CoV-2 infection tends to aggravate bone-forming capacity. The deficiency of ACE2, which caused by the invasion of virus, may lead to a decreased bone matrix and early muscle disorder. Deficiency of ACE2 in Bone-4 Marrow-Derived Cells Increases Expression of TNF-α in Adipose Stromal Cells and Augments Glucose Intolerance in Obese C57BL/6 Mice -7) axis in kidney and cardiac inflammation and fibrosis Pulmonary Angiotensin-Converting Enzyme 2 (ACE2) and Inflammatory Lung Disease Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cells Angiotensin 1-7 alleviates agingassociated muscle weakness and bone loss, but is not associated with accelerated aging in ACE2-knockout mice The ACE-2/Ang1-7/Mas cascade enhances bone structure and metabolism following angiotensin-II type 1 receptor blockade Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction This study was supported by the National Natural Science Foundation of China (81873991, 81771885, 81672238, 81472077, 81572183, 91849114 and 81472105) The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.