In:
The FASEB Journal, Wiley, Vol. 37, No. 8 ( 2023-08)
Abstract:
A new target that stimulates bone formation is needed to overcome limitations of current anti‐osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase‐like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3‐E1 cells and/or calvaria osteoblasts were treated with recombinant N‐terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen‐activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre‐treatment with a TGF‐β receptor inhibitor. Under H 2 O 2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H 2 O 2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase‐9 activities. rmACLP (N)‐stimulated osteoblast survival was reversed by pre‐treatment with a p38 inhibitor, a TGF‐β‐receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H 2 O 2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti‐oxidant genes such as Sod2 , Trx2 , and Prx5 . In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF‐β receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fj.202300140R
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
1468876-1
detail.hit.zdb_id:
639186-2
SSG:
12
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