Methods for improving mechanical properties of a tissue or for regenerating an injured or diseased tissue
The present invention relates to enhancing mechanical properties of tissue such as collagenous or collagen-containing or elastin-containing tissue (e.g., tendons, ligaments, and cartilage) and treating related musculoskeletal and non-musculoskeletal conditions or injuries.
1. A method (i) for improving a mechanical property of a tissue or a component thereof in a subject or (ii) for regenerating an injured or diseased tissue or a component thereof in a subject or (iii) for developing embryonic/fetal tissue or a component thereof in a subject, comprising: (a) applying a mechanical stimulation to the tissue or cells therein, and (b) increasing the level of lysyl oxidase (LOX) activity in the tissue by delivering to the tissue a LOX polypeptide, a pre-proLOX polypeptide, a proLOX polypeptide, a nucleic acid encoding one or more of the polypeptides, or a viral particle having the nucleic acid.
2. The method of claim 1 , wherein said mechanical stimulation comprises one or more of a dynamic stimulation, a cyclic stimulation, a static stimulation, a deformation, a tensile stimulation, a compressive stimulation, a torsion stimulation, a shear stimulation, substrate stiffness, a mechanical loading, a static loading, a dynamic loading, a cyclic loading, a compression, shear, torsion, and deformation.
3. The method of claim 1 , wherein the tissue is a natural tissue, an engineered tissue, an embryonic tissue, a postnatal tissue, a tissue in vitro, or a tissue in vivo.
4. The method of claim 3 , wherein the tissue is a collagenous or collagen-containing tissue.
5. The method of claim 1 , wherein the mechanical property is selected from the group consisting of elastic modulus, tensile strength, torsional strength, elongation to break, hardness, compressive strength, burst strength, toughness, impact strength, torsion, failure load, and stiffness.
6. The method of claim 1 , wherein the LOX activity is an activity of a LOX polypeptide or a LOX-like (LOXL) polypeptide.
7. The method of claim 1 , further comprising administering a population of cells to the tissue.
8. The method of claim 7 , wherein the cells are (i) collagen-producing or elastin-producing cells or progenitor cells thereof or (ii) engineered to release a specific factor that directly or indirectly promotes LOX/LOXL or pro-LOX/pro-LOXL gene expression, LOX/LOXL or pro-LOX/pro-LOXL protein expression, or LOX/LOXL enzyme activity.
9. The method of claim 1 , wherein this tissue is a tendon tissue or a ligament tissue.
10. The method of claim 1 , wherein the tissue is a healthy tissue.
11. The method of claim 1 , wherein the mechanical stimulation increases the level of LOX activity in the tissue.