Details

Autor(en) / Beteiligte

• Yamaguchi, Hiroyuki
• Li, Margaret
• Kitami, Megumi
• Swaminathan, Sowmya
• Mishina, Yuji
• Komatsu, Yoshihiro

Titel

Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification

Ist Teil von

• Biochemical and biophysical research communications, 2023-12, Vol.688, p.149147-149147, Article 149147

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Heterotopic ossification (HO) is abnormal bone growth in soft tissues that results from injury, trauma, and rare genetic disorders. Bone morphogenetic proteins (BMPs) are critical osteogenic regulators which are involved in HO. However, it remains unclear how BMP signaling interacts with other extracellular stimuli to form HO. To address this question, using the Cre-loxP recombination system in mice, we conditionally expressed the constitutively activated BMP type I receptor ALK2 with a Q207D mutation (Ca-ALK2) in Cathepsin K-Cre labeled tendon progenitors (hereafter “Ca-Alk2:Ctsk-Cre”). Ca-Alk2:Ctsk-Cre mice were viable but they formed spontaneous HO in the Achilles tendon. Histological and molecular marker analysis revealed that HO is formed via endochondral ossification. Ectopic chondrogenesis coincided with enhanced GLI1 production, suggesting that elevated Hedgehog (Hh) signaling is involved in the pathogenesis of HO. Interestingly, focal adhesion kinase, a critical mediator for the mechanotransduction pathway, was also activated in Ca-Alk2:Ctsk-Cre mice. Our findings suggest that enhanced BMP signaling may elevate Hh and mechanotransduction pathways, thereby causing HO in the regions of the Achilles tendon. •Cathepsin K-Cre-driven enhanced BMP signaling induces heterotopic ossification (HO) in mice.•Ectopic endochondral ossification is associated with the pathogenesis of HO in the tendon.•Elevated hedgehog and mechanotransduction pathways are associated with HO in mice.