What is the Role of Bone marrow Adipocytes in the Pathological Bone Remodeling Processes of the Trapezio-metacarpal Osteoarthritis
Mauro Maniglio, MD.1, Lea Loisay, PhD2, Thomas Hügle, Prof.1 and Jeroen Geurts, Prof.1, (1)CHUV, Lausanne, Switzerland, (2)CHUV, Lausanne, Schweiz, Switzerland
Bone remodeling processes, such as subchondral bone sclerosis, osteophyte formation and bone marrow lesions are radiographic hallmarks of thumb base osteoarthritis (CMC-1 OA). High body mass index (BMI) and obesity were found as major risk factors for CMC-1 OA . As mediators of this increased risk of OA at a non-weight bearing joint, adipose tissue-derived systemic factors, such as lipids and adipokines, have been proposed. This hypothesis is supported by the fact that alterations in systemic lipid levels have been found to be associate with the severity of hand OA . However, the role of subchondral marrow adipose tissue in the development and progression of CMC-1 OA is unknown.
Our objective is to determine whether bone marrow adipocyte (BMAd) size, as a surrogate marker of adipocyte lipolysis and (dys)function, differed as a function of the extent of subchondral bone remodeling and BMI in CMC-1 OA.
Material and Methods:
Trapezium and/or metacarpal bone resections were harvested from 14 consecutive CMC-1 OA patients (9 female, 63±11 years, 26±6 kg/m2) undergoing trapezectomy or joint replacement arthroplasty. BMAd size, osteoblast numbers and OA severity were determined by histomorphometry. Expression of the lipolytic enzyme monoacylglycerol lipase (MGLL) on bone marrow-resident cells was assessed by immunohistochemistry. The lipidome of the different specimens were also examined and correlated with markers of bone turnover.
Eight out of fourteen specimens displayed regions of increased bone remodeling and osteoblast
numbers, which were classified by histology as subchondral sclerosis (n=6) and central osteophyte
formation (n=2) (Fig.1). BMAd size was significantly reduced (p=0.02) in the remodeling (839±319 μm2)
compared with non-remodeling regions (1438±578 μm2), independent of OA severity (Fig. 2). BMAd size
was positively correlated with BMI (r=0.63, p=0.03), but in non-remodeling regions only. MGLL was
differentially expressed both in terms of quantity and cell type in non-remodeling and remodeling
regions (Fig. 3). Surprisingly, MGLL was strongly expressed by osteoblasts and blood vessels rather
than mature BMAd in remodelling regions. A correlations (Pearson's) between Procollagen I as a marker of bone turnover, Triglycerides (0.94) and Glycerol (0.92) was found in the explantated specimens.
Collectively, these data suggest that BMAd properties in the CMC-1 joint may be BMI-dependent.
Increased lipolytic activity in subchondral bone marrow adipose tissue may be fueling pathologic
bone formation in CMC-1 OA.
 van Beest et al. Osteoarthritis Cartilage 2018
 Rydberg et al. RMD Open 2020
 Loef et al. Osteoarthritis Cartilage 2022
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