Parathyroid hormone [1-34] improves articular cartilage surface architecture and integration and subchondral bone reconstitution in osteochondral defects in vivo.
OBJECTIVE
The 1-34 amino acid segment of the parathyroid hormone (PTH [1-34]) mediates anabolic effects in chondrocytes and osteocytes. The aim of this study was to investigate whether systemic application of PTH [1-34] improves the repair of non-osteoarthritic, focal osteochondral defects in vivo.


METHODS
Standardized cylindrical osteochondral defects were bilaterally created in the femoral trochlea of rabbits (n = 8). Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to the treatment group (n = 4) for 6 weeks, controls (n = 4) received saline. Articular cartilage repair was evaluated by macroscopic, biochemical, histological and immunohistochemical analyses. Reconstitution of the subchondral bone was assessed by micro-computed tomography. Effects of PTH [1-34] on synovial membrane, apoptosis, and expression of the PTH receptor (PTH1R) were determined.


RESULTS
Systemic PTH [1-34] increased PTH1R expression on both, chondrocytes and osteocytes within the repair tissue. PTH [1-34] ameliorated the macro- and microscopic aspect of the cartilaginous repair tissue. It also enhanced the thickness of the subchondral bone plate and the microarchitecture of the subarticular spongiosa within the defects. No significant correlations were established between these coexistent processes. Apoptotic levels, synovial membrane, biochemical composition of the repair tissue, and type-I/II collagen immunoreactivity remained unaffected.


CONCLUSIONS
PTH [1-34] emerges as a promising agent in the treatment of focal osteochondral defects as its systemic administration simultaneously stimulates articular cartilage and subchondral bone repair. Importantly, both time-dependent mechanisms of repair did not correlate significantly at this early time point and need to be followed over prolonged observation periods.
Center of Experimental Orthopaedics, Saarland University, Homburg/Saar, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany. patrick.orth@uks.eu
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Orth
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Cucchiarini
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Zurakowski
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Menger
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Kohn
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Madry
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D007273:Injections, Intramuscular; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D055114:X-Ray Microtomography / Q000379:methods
D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D003094:Collagen; D002118:Calcium