软骨下骨髓脂肪组织脂解调节手部骨关节炎中的骨形成。

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

作者信息

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

机构信息

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.

Rheumatology, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.

出版信息

Osteoarthritis Cartilage. 2025 Mar;33(3):322-329. doi: 10.1016/j.joca.2024.12.005. Epub 2024 Dec 24.

DOI:10.1016/j.joca.2024.12.005

PMID:39725154

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 carpometacarpal (CMC-1) and distal interphalangeal joint 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 µm, [-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.

摘要

目的

骨髓脂肪组织（BMAT）正逐渐成为骨形成和能量代谢的重要调节因子。BMAT的脂解作用释放甘油和脂肪酸底物，这些底物被成骨细胞分解代谢。在此，我们研究了BMAT脂解是否参与手部骨关节炎（OA）的软骨下骨形成。

方法

在掌指关节（CMC-1）和远端指间关节OA的临床标本中研究软骨下BMAT脂解和骨髓脂肪细胞（BMAd）形态。比较低骨形成区域和高骨形成区域的BMAd大小、成骨细胞数量以及脂解酶（ATGL、磷酸化HSL、MGLL）的表达。在骨软骨外植体中测量游离脂肪酸、甘油和骨生物标志物。

结果

软骨下BMAd大小与BMI呈正相关（r = 0.60，[0.082,0.87]），在高骨形成区域减小（-1149 µm，[-1977,-726.2]）。成骨细胞数量与BMAd大小呈负相关（r = -0.48，[-0.73,-0.12]）。所有脂解酶在BMAd和活化的成骨细胞中均有表达，且高骨形成区域中ATGL（+2.26% [0.19,3.47]）、磷酸化HSL（+1.57% [0.31,6.48]）和MGLL（+4.04% [1.09,5.69]）的面积百分比增加。分泌的甘油水平而非游离脂肪酸与骨形成标志物I型前胶原（rho = 0.90）和碱性磷酸酶（rho = 0.78）相关。