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Publication : The Overexpression of BMP Type I Receptor ALK3 Has a Protective Effect in Degenerative Disc Disease in a Mouse Model.

First Author  Maqsoodi N Year  2026
Journal  Spine (Phila Pa 1976) Volume  51
Issue  12 Pages  E313-E320
PubMed ID  40955701 Mgi Jnum  J:392825
Mgi Id  MGI:8436695 Doi  10.1097/BRS.0000000000005502
Citation  Maqsoodi N, et al. (2026) The Overexpression of BMP Type I Receptor ALK3 Has a Protective Effect in Degenerative Disc Disease in a Mouse Model. Spine (Phila Pa 1976) 51(12):E313-E320
abstractText  STUDY DESIGN: Basic science. OBJECTIVE: The goal of this study was to investigate a novel therapeutic approach for treating degenerative disc disease (DDD) by enhancing anabolic signaling through ALK3 overexpression in the intervertebral disc, using a mouse tail compression model. SUMMARY OF BACKGROUND DATA: Our previous data showed induction of BMP/Smad signaling in intervertebral disc tissue of DDD patients. The role of such induction is not fully understood, but previous literature indicates mostly protective effects of exogenous BMPs against DDD. METHODS: ALK3 transgenic mice (ALK3 TG ) were crossed to tamoxifen-inducible Aggrecan-Cre (Acan-Cre ERt2 ) mice to assess the protective effect of tissue-specific ALK3 overexpression using a tail compression device in the caudal vertebrae to induce DDD. Cre+;ALK3 TG (GOF, n=40) and Cre-;ALK3 TG (Cre- control, n=40) mice were used. At four and eight weeks, tails were harvested and analyzed with histomorphometry and micro-computed tomography. RESULTS: In the male cohort, GOF mice showed significantly greater proteoglycan content compared with Cre- controls at four and eight weeks after tail compression. There was no difference proteoglycan content in the female compression cohort at either time point. In the male cohort, GOF mice trended towards having a larger disc area than Cre- controls at four weeks after tail compression, but no difference was observed at eight weeks. In the female cohort, disc area was significantly larger in GOF mice compared with Cre- controls at four and eight weeks after tail compression. CONCLUSIONS: Using a tail compression device to model DDD, we found that ALK3 overexpression in aggrecan-expressing disc cells enhanced BMP signaling and maintained higher proteoglycan content in male mice and increased disc area in female mice.
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