Potential targets for pharmacologic therapies for prevention of PTA

Cecilia Pascual-Garrido, Susan Chubinskaya

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

4 Scopus citations

Abstract

Joint injuries are common, especially among young adults of age 18–44 years old. They are accompanied by a cascade of events that increase the risk of post-traumatic osteoarthritis (PTOA). Therefore, understanding biological responses that predispose to PTOA should help in determining treatment modalities to delay and/or prevent the onset and progression of the disease. The vast majority of the literature pointed to chondrocyte death and apoptosis, inflammation and matrix damage/fragmentation being the earliest events that follow joint trauma. Together these events lead to the development of OA-like focal cartilage lesions that if untreated have a tendency to expand and progress to fully developed disease. Currently, the only treatments available for joint trauma are surgical interventions. Experimental biologic approaches involve engineering of cartilage with the use of cells (stem cells or chondrocytes), juvenile or adult cartilage pieces, scaffolds and various polymeric matrices. The major challenge for all of them is regeneration of normal functional mature hyaline cartilage that can sustain the load, resist compression, and most importantly, integrate with the host tissue. If the tissue is spontaneously repaired it fails to reproduce original structure and function and thus, may be more susceptible to reinjury. Thus, there is a critical need to develop novel molecular mechanism-based therapeutic approaches to biologic chondral and/or osteochondral repair. The focus of this review is on the earliest molecular and cellular manifestations of injury that can be grouped based on the following therapeutic options for PTOA: chondroprotection, anti-inflammatory, matrix protection, and matrix remodeling/matrix synthesis.

Original languageEnglish
Title of host publicationPost-Traumatic Arthritis
Subtitle of host publicationPathogenesis, Diagnosis and Management
PublisherSpringer US
Pages331-342
Number of pages12
ISBN (Electronic)9781489976062
ISBN (Print)9781489976055
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Anabolic responses
  • Anti-inflammatory
  • Chondroprotection
  • Matrix degradation
  • Post-traumatic osteoarthritis
  • Repair

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