Subchondral bone marrow adipose tissue lipolysis regulates bone formation in hand osteoarthritis

Mauro Maniglio; Léa Loisay; Diego de Haro; Alexander Antoniadis; Thomas Hügle; Jeroen Geurts

doi:10.1016/j.joca.2024.12.005

Subchondral bone marrow adipose tissue lipolysis regulates bone formation in hand osteoarthritis

Osteoarthritis Cartilage. 2024 Dec 24:S1063-4584(24)01504-8. doi: 10.1016/j.joca.2024.12.005. Online ahead of print.

Authors

Mauro Maniglio¹, Léa Loisay², Diego de Haro², Alexander Antoniadis³, Thomas Hügle², Jeroen Geurts⁴

Affiliations

¹ Plastic and Hand Surgery, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland; Department of Hand Surgery, Balgrist University Clinic, Zürich, Switzerland.
² Rheumatology, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne,Switzerland.
³ Orthopaedics, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.
⁴ Rheumatology, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne,Switzerland. Electronic address: Jeroen.Geurts@chuv.ch.

PMID: 39725154
DOI: 10.1016/j.joca.2024.12.005

Abstract

Objective: Bone marrow adipose tissue (BMAT) is emerging as an important regulator of bone formation and energy metabolism. Lipolysis of BMAT releases glycerol and fatty acid substrates that are catabolized by osteoblasts. Here, we investigated whether BMAT lipolysis is involved in subchondral bone formation in hand osteoarthritis (OA).

Methods: Subchondral BMAT lipolysis and bone marrow adipocyte (BMAd) morphology were studied in clinical specimens of carpo-metacarpal (CMC1) and distal interphalangeal joint (DIP) OA. BMAd size, osteoblast numbers and expression of lipolysis enzymes (ATGL, phospho-HSL, MGLL) were compared between regions of low and high bone formation. Free fatty acids, glycerol and bone biomarkers were measured in osteochondral explants.

Results: Subchondral BMAd size was positively correlated with BMI (r = 0.60, [0.082,0.87]) and reduced in regions of high bone formation (-1149 µm², [-1977,-726.2]). Osteoblast numbers were negatively correlated with BMAd size (r = -0.48, [-0.73,-0.12]). All lipolysis enzymes were expressed in both in BMAds and activated osteoblasts and the area percentages of ATGL (+2.26% [0.19,3.47]), phospho-HSL (+1.57% [0.31,6.48]) and MGLL (+4.04% [1.09,5.69]) were increased in regions of high bone formation. Secreted glycerol levels, but not free fatty acids, were correlated with bone formation markers pro-collagen type I (rho = 0.90) and alkaline phosphatase (rho = 0.78).

Conclusion: Our findings reveal a previously unrecognized role of BMAT lipolysis in regulating bone formation in hand OA, which may be modulated by BMI.

Keywords: Bone marrow adipose tissue; bone; hand OA; lipolysis; osteoblast.