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Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.

Publication ,  Journal Article
Sampson, ER; Hilton, MJ; Tian, Y; Chen, D; Schwarz, EM; Mooney, RA; Bukata, SV; O'Keefe, RJ; Awad, H; Puzas, JE; Rosier, RN; Zuscik, MJ
Published in: Sci Transl Med
September 21, 2011

There is no disease-modifying therapy for osteoarthritis, a degenerative joint disease that is projected to afflict more than 67 million individuals in the United States alone by 2030. Because disease pathogenesis is associated with inappropriate articular chondrocyte maturation resembling that seen during normal endochondral ossification, pathways that govern the maturation of articular chondrocytes are candidate therapeutic targets. It is well established that parathyroid hormone (PTH) acting via the type 1 PTH receptor induces matrix synthesis and suppresses maturation of chondrocytes. We report that the PTH receptor is up-regulated in articular chondrocytes after meniscal injury and in osteoarthritis in humans and in a mouse model of injury-induced knee osteoarthritis. To test whether recombinant human PTH(1-34) (teriparatide) would inhibit aberrant chondrocyte maturation and associated articular cartilage degeneration, we administered systemic teriparatide (Forteo), a Food and Drug Administration-approved treatment for osteoporosis, either immediately after or 8 weeks after meniscal/ligamentous injury in mice. Knee joints were harvested at 4, 8, or 12 weeks after injury to examine the effects of teriparatide on cartilage degeneration and articular chondrocyte maturation. Microcomputed tomography revealed increased bone volume within joints from teriparatide-treated mice compared to saline-treated control animals. Immediate systemic administration of teriparatide increased proteoglycan content and inhibited articular cartilage degeneration, whereas delayed treatment beginning 8 weeks after injury induced a regenerative effect. The chondroprotective and chondroregenerative effects of teriparatide correlated with decreased expression of type X collagen, RUNX2 (runt-related transcription factor 2), matrix metalloproteinase 13, and the carboxyl-terminal aggrecan cleavage product NITEGE. These preclinical findings provide proof of concept that Forteo may be useful for decelerating cartilage degeneration and inducing matrix regeneration in patients with osteoarthritis.

Duke Scholars

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 21, 2011

Volume

3

Issue

101

Start / End Page

101ra93

Location

United States

Related Subject Headings

  • Tibial Meniscus Injuries
  • Teriparatide
  • Serrate-Jagged Proteins
  • Regenerative Medicine
  • Regeneration
  • Receptor, Parathyroid Hormone, Type 1
  • Proteoglycans
  • Osteophyte
  • Osteoarthritis
  • Mice, Inbred C57BL
 

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Sampson, E. R., Hilton, M. J., Tian, Y., Chen, D., Schwarz, E. M., Mooney, R. A., … Zuscik, M. J. (2011). Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med, 3(101), 101ra93. https://doi.org/10.1126/scitranslmed.3002214
Sampson, Erik R., Matthew J. Hilton, Ye Tian, Di Chen, Edward M. Schwarz, Robert A. Mooney, Susan V. Bukata, et al. “Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.Sci Transl Med 3, no. 101 (September 21, 2011): 101ra93. https://doi.org/10.1126/scitranslmed.3002214.
Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, et al. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med. 2011 Sep 21;3(101):101ra93.
Sampson, Erik R., et al. “Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis.Sci Transl Med, vol. 3, no. 101, Sept. 2011, p. 101ra93. Pubmed, doi:10.1126/scitranslmed.3002214.
Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O’Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med. 2011 Sep 21;3(101):101ra93.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

September 21, 2011

Volume

3

Issue

101

Start / End Page

101ra93

Location

United States

Related Subject Headings

  • Tibial Meniscus Injuries
  • Teriparatide
  • Serrate-Jagged Proteins
  • Regenerative Medicine
  • Regeneration
  • Receptor, Parathyroid Hormone, Type 1
  • Proteoglycans
  • Osteophyte
  • Osteoarthritis
  • Mice, Inbred C57BL