title: Substance P enhances collagen remodeling and MMP-3 expression by human tenocytes.
abstract: The loss of collagen organization is considered a hallmark histopathologic feature of tendinosis. At the cellular level, tenocytes have been shown to produce signal substances that were once thought to be restricted to neurons. One of the main neuropeptides implicated in tendinosis, substance P (SP), is known to influence collagen organization, particularly after injury. The aim of this study was to examine the influence of SP on collagen remodeling by primary human tendon cells cultured in vitro in three-dimensional collagen lattices. We found that SP stimulation led to an increased rate of collagen remodeling mediated via the neurokinin-1 receptor (NK-1 R), the preferred cell receptor for SP. Gene expression analysis showed that SP stimulation resulted in significant increases in MMP3, COL3A1 and ACTA2 mRNA levels in the collagen lattices. Furthermore, cyclic tensile loading of tendon cell cultures along with the administration of exogenous SP had an additive effect on MMP3 expression. Immunoblotting confirmed that SP increased MMP3 protein levels via the NK-1 R. This study indicates that SP, mediated via NK-1 R, increases collagen remodeling and leads to increased MMP3 mRNA and protein expression that is further enhanced by cyclic mechanical loading.
authors: Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Gloria
authors: G
authors: Fong
authors: Ludvig J
authors: LJ
authors: Backman
authors: David A
authors: DA
authors: Hart
authors: Patrik
authors: P
authors: Danielson
authors: Bob
authors: B
authors: McCormack
authors: Alex
authors: A
authors: Scott
mesh_terms: D000125:Achilles Tendon / Q000166:cytology* / Q000502:physiology; D000199:Actins / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology; D061251:Primary Cell Culture; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology; D052256:Tendinopathy / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C439971:COL3A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D013373:Substance P; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1