An anatomical role for adipocytes in pathological and non-pathological bone formation

Shepherd, Rebecca (2021) An anatomical role for adipocytes in pathological and non-pathological bone formation. PhD thesis, UNSPECIFIED.

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Abstract

Abstract Rebecca Frances Shepherd; An anatomical role for adipocytes in pathological and non- pathological bone formation; October 2020 Background: Trabecular excrescences are novel microscopic bone-like formations that have been found in patients with osteoarthropathies (OA). Excrescence formation is found associated with the presence of bone marrow adipocytes (BMAds) and the absence of bone lining cells. BMAds are ‘yellow’ adipocytes with a distinct lipid metabolism and function to adipocytes found elsewhere in the mammalian body. Hypothesis: BMAds are contributing to the formation of bone-like structures, a concept that is inconsistent with the paradigm of osteoclast-osteoblast coupled remodelling. This study investigated the relationship between the formation of trabecular excrescences and BMAds. Method: Joint samples (20 non-OA, 20 OA) were obtained with informed patient consent. A subset of the samples (15 non-OA, 14 OA) had BMAds prepared for flow cytometric analysis. BMAds were gated by size, absence of haemopoietic cell markers, viability and lipid content. Cell markers for adiponectin (ACRP30), uncoupling protein 1 (UCP1) and myogenic factor 5 (MYF5), were used to distinguish between adipocyte populations. All joint samples were decalcified and processed for histology. Sections underwent immunohistochemistry (IHC) for collagen I, collagen VI (COLVI), ACRP30, UCP1 and MYF5. Results: Excrescences were found in both patient groups. IHC identified COLVI within the extracellular matrix of the newly formed excrescences. Flow cytometry identified UCP1 containing BMAds. The histological study confirmed the presence of UCP1+ multilocular lipid containing adipocytes. iv Conclusion: This study has demonstrated the presence of UCP1+ multilocular BMAds, a phenotype previously only identified in brown/beige adipocytes. Skeletal disorders are a wide-ranging group of conditions and a major cause of morbidity worldwide. By understanding the role adipocytes play in trabecular bone we can potentially identify future therapeutic targets.