| First Author | Wang X | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 2 | Pages | 846-860 |
| PubMed ID | 29355842 | Mgi Jnum | J:257521 |
| Mgi Id | MGI:6118037 | Doi | 10.1172/JCI96186 |
| Citation | Wang X, et al. (2018) Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease. J Clin Invest 128(2):846-860 |
| abstractText | Enthesopathy is a disorder of bone, tendon, or ligament insertion. It represents one-fourth of all tendon-ligament diseases and is one of the most difficult tendon-ligament disorders to treat. Despite its high prevalence, the exact pathogenesis of this condition remains unknown. Here, we show that TGF-beta was activated in both a semi-Achilles tendon transection (SMTS) mouse model and in a dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations of active TGF-beta recruited mesenchymal stromal stem cells (MSCs) and led to excessive vessel formation, bone deterioration, and fibrocartilage calcification. Transgenic expression of active TGF-beta1 in bone also induced enthesopathy with a phenotype similar to that observed in SMTS and DI mice. Systemic inhibition of TGF-beta activity by injection of 1D11, a TGF-beta-neutralizing antibody, but not a vehicle antibody, attenuated the excessive vessel formation and restored uncoupled bone remodeling in SMTS mice. 1D11-treated SMTS fibrocartilage had increased proteoglycan and decreased collagen X and matrix metalloproteinase 13 expression relative to control antibody treatment. Notably, inducible knockout of the TGF-beta type II receptor in mouse MSCs preserved the bone microarchitecture and fibrocartilage composition after SMTS relative to the WT littermate controls. Thus, elevated levels of active TGF-beta in the enthesis bone marrow induce the initial pathological changes of enthesopathy, indicating that TGF-beta inhibition could be a potential therapeutic strategy. |
