title: Treatment with rhBMP12 or rhBMP13 increase the rate and the quality of rat Achilles tendon repair.
abstract: Tendon injuries that result in partial or complete tears often come from chronic, repetitive use, or from sudden trauma. In some cases, torn tendons can be repaired, but such repairs often fail to completely restore tendon function. We used global gene expression profiling and histological examination to study tendon repair to elucidate key molecular processes that regulate the rate and quality of tissue restoration. Using a rat Achilles tendon transection model, tissue was collected at 3, 7, 10, and 15 days postinjury. The pattern of gene expression in the repairing tissue paralleled the healing phases of inflammation, matrix formation, and matrix reorganization. Newly formed repaired tissue is characterized by cells expressing many genes associated with tendon formation, thereby potentially distinguishing this repair tissue from other types of repair or scar tissue. Addition of recombinant human bone morphogenic protein (rhBMP)12 or rhBMP13, also known as growth and differentiation factors (GDFs) 6 and 7, 1 day after injury yielded increases in tissue volume, rate of cellular infiltration, and in changes in levels of key mRNAs involved in tendon repair. Altogether, our results indicate that rhBMP12 or rhBMP13 enhance the rate of tendon repair. A better understanding of the key molecular regulators of tendon repair could lead to the development of new therapies for tendon injuries and the identification of diagnostic markers that indicate the status of tendon repair after injury.
authors.affiliation: Tissue Repair, Pfizer Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. scott.jelinsky@pfizer.com
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jelinsky
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Debra
authors.initials: D
authors.lastname: Ellis
authors.forename: Joanne
authors.initials: J
authors.lastname: Archambault
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: St Andre
authors.forename: Carl
authors.initials: C
authors.lastname: Morris
authors.forename: Howard
authors.initials: H
authors.lastname: Seeherman
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D055431:Growth Differentiation Factor 6 / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D055412:Growth Differentiation Factors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D013708:Tendon Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D019485:Bone Morphogenetic Proteins; C525906:GDF6 protein, human; C499470:GDF7 protein, human; C525908:Gdf6 protein, rat; C499472:Gdf7 protein, rat; D055431:Growth Differentiation Factor 6; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins