The Effects of Corticosteroid Administration and Treadmill Exercise on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in Rats

Abstract

We aimed to investigate the effects of short-term corticosteroid administration after anterior cruciate ligament (ACL) reconstruction on marrow adipose tissue (MAT) and trabecular bone mass, as well as to examine whether treadmill exercise can mitigate MAT increase and trabecular bone deterioration caused by corticosteroid. ACL-reconstructed rats were divided into groups: no intervention, daily treadmill exercise (60 min/day), administration of the steroidal drug dexamethasone (250 μg/kg on days 0-5, 7, and 9 post-operatively), or dexamethasone administration combined with treadmill exercise. Untreated rats were served as controls. At day 10 or 30 post-operatively, histological assessments were performed in the proximal tibial epiphysis. MAT accumulation and trabecular bone loss were observed after ACL reconstruction. Dexamethasone promoted MAT accumulation at day 10 post-operatively but did not affect the trabecular bone loss. The MAT accumulation caused by dexamethasone reversed within 21 days after discontinuation. Treadmill exercise did not influence the changes in the MAT and trabecular bone areas. Short-term corticosteroid administration after ACL reconstruction promoted MAT accumulation while not affecting trabecular bone area. The MAT accumulation resulting from corticosteroid administration was reversible after discontinuation. Treadmill exercise could not mitigate the accumulation of MAT caused by corticosteroid administration and did not affect trabecular bone area.

Keywords: ACL reconstruction; bone; exercise; marrow adipose tissue; steroids.

Fig. 1.

Experimental protocol. ACLR, anterior cruciate ligament reconstruction; T, treadmill exercise; D, dexamethasone administration.

Fig. 2.

Histological features in the proximal tibial epiphysis. Representative images of Safranin-O Fast Green-stained sections from the control (A, F), ACLR (B, G), ACLR + T (C, H), ACLR + D (D, I), and ACLR + DT (E, J) groups. A–E and F–J represent at day 10 and 30 post-operatively, respectively. Bars = 500 μm. ACLR, anterior cruciate ligament reconstruction; T, treadmill exercise; D, dexamethasone administration.

Fig. 3.

Trabecular bone area, osteoclast surface length, and bone marrow adiposity. (A) Trabecular bone area, (B), osteoclast surface length, (C) adipocyte number, (D) adipocyte size, and (E) marrow adipose tissue area. Values are mean ± standard deviation. Different letters indicate statistically significant differences between groups at same timepoint, whereby groups not sharing the same letter are significantly different from one another. *: significant difference compared with day 10 post-operatively. ACLR, anterior cruciate ligament reconstruction; T, treadmill exercise; D, dexamethasone administration.

Fig. 4.

Osteoclasts in the proximal tibial epiphysis. Representative images of tartrate-resistant acid phosphatase-stained sections from the control (A, F), ACLR (B, G), ACLR + T (C, H), ACLR + D (D, I), and ACLR + DT (E, J) groups. A–E and F–J represent at day 10 and 30 post-operatively, respectively. Osteoclasts are stained in purple. Bars = 250 μm. ACLR, anterior cruciate ligament reconstruction; T, treadmill exercise; D, dexamethasone administration.

Fig. 5.

Correlations between trabecular bone area and marrow adipose tissue area (A), osteoclast surface length and marrow adipose tissue area (B), and osteoclast surface length and trabecular bone area (C). A moderate negative correlation was observed between trabecular bone area and marrow adipose tissue area (A). A weak positive correlation was observed between osteoclast surface length and marrow adipose tissue area (B). A weak negative correlation was observed between osteoclast surface length and trabecular bone area (C). ACLR, anterior cruciate ligament reconstruction; T, treadmill exercise; D, dexamethasone administration.