Protein-Degrading Enzymes in Osteoarthritis

Peidong Pu; Ma Qingyuan; Wang Weishan; Han Fei; Ma Tengyang; Zhou Weiping; Zhu Zhoujun; Wang Mengyu; Wang Chao; Shi Chong

doi:10.1055/a-1019-8117

Zeitschrift für Orthopädie und Unfallchirurgie, Table of Contents

Z Orthop Unfall 2021; 159(01): 54-66
DOI: 10.1055/a-1019-8117

Original Article

Protein-Degrading Enzymes in Osteoarthritis

Proteolytische Enzyme in der Osteoarthritis

Peidong Pu‡

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Ma Qingyuan‡

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Wang Weishan

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Han Fei

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Ma Tengyang

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Zhou Weiping

²Xinjiang Military Region 69337 Unit Health Center, China

,

Zhu Zhoujun

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Wang Mengyu

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Wang Chao

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

,

Shi Chong

¹Department of Orthopaedics, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, China

› Author Affiliations

Abstract

Objective TGFβ1 plays an important role in the metabolism of articular cartilage and bone; however, the pathological mechanism and targets of TGFβ1 in cartilage degradation and uncoupling of subchondral bone remodeling remain unclear. Therefore, in this study, we investigated the relationship between TGFβ1 and major protein-degrading enzymes, and evaluated the role of high levels of active TGFβ1 in the thickening of subchondral bone and calcification of articular cartilage.

Materials and Methods The expression of TGFβ1 and protein-degrading enzymes in clinical samples of articular cartilage and subchondral bone obtained from the knee joint of patients with osteoarthritis was detected by immunohistochemistry. The expression levels of TGFβ1, MMP-3, MMP-13 and IL-1β in cartilage and subchondral bone tissues were detected by absolute real-time quantitative RT-PCR. The expression of TGFβ1, nestin and osterix in subchondral bone was detected by Western blot analysis and immunohistochemistry. The degree of subchondral bone thickening was determined by micro-computed tomography (CT) imaging.

Results Expression of TGFβ1 and cartilage-degrading enzymes was higher in the cartilage-disrupted group than that in the intact group. Furthermore, expression of TGFβ1, nestin and osterix was significantly higher in the OA group than that in the control group. Micro-CT imaging showed that in the OA group, the subchondral bone plate is thickened and the density is increased. The trabecular bone structure is thick plate-like structure, the thickness of the trabecular bone is increased and the gap is small.

Conclusions The data suggest that highly active TGFβ1 activates the expression of cartilage-degrading enzymes. Abnormally activated TGFβ1 may induce formation of the subchondral bone and expansion of the calcified cartilage area, eventually leading to degradation of the cartilage tissue.

Zusammenfassung

Ziel TGFβ1 spielt eine wichtige Rolle im Stoffwechsel von Gelenkknorpel und Knochen; jedoch bleiben der pathologische Mechanismus und die Ziele von TGFβ1 beim Knorpelabbau und Entkopplung des subchondralen Knochenumbaus unklar. Daher untersuchten wir in dieser Studie die Beziehung zwischen TGFβ1 und wichtigen proteinabbauenden Enzymen und der Rolle hoher Konzentrationen an aktivem TGFβ1 bei der Verdickung des subchondralen Knochens und Verkalkung des Gelenkknorpels.

Materialien und Methoden Die Expression von TGFβ1 und der Abbau von Enzymen in klinischen Proben von Gelenkknorpel und subchondralen Knochen aus dem Kniegelenk von Patienten mit Arthrose wurden immunhistochemisch nachgewiesen. Die Expressionsniveaus von TGFβ1, MMP-3, MMP-13 und IL-1β in Knorpel- und subchondralen Knochengeweben wurden durch absolute quantitative RT-PCR in Echtzeit nachgewiesen. Die Expression von TGFβ1, Nestin und Osterix im subchondralen Knochen wurde durch Western-Blot-Analyse und Immunhistochemie nachgewiesen. Der Grad der subchondralen Knochenverdickung wurde durch Mikrocomputertomografie (CT) bestimmt.

Ergebnisse Die Expression von TGFβ1 und knorpelabbauenden Enzymen war in der Gruppe mit Knorpelstörungen höher als in der intakten Gruppe. Weiterhin war die Expression von TGFβ1, Nestin und Osterix in der OA-Gruppe signifikant höher als in der Kontrollgruppe. Die Mikro-CT-Bildgebung zeigte, dass in der OA-Gruppe die subchondrale Knochenplatte verdickt und die Dichte erhöht ist. Die trabekuläre Knochenstruktur ist dick plättchenförmig, die Dicke des Trabekelknochens erhöht und die Lücke ist klein.

Schlussfolgerungen Die Daten legen nahe, dass hochaktives TGFβ1 die Expression von knorpelabbauenden Enzymen aktiviert. Ungewöhnlich aktiviertem TGFβ1 kann die Bildung des subchondralen Knochens und Ausdehnung des verkalkten Knorpelbereichs induzieren, was zu einem Abbau des Knorpelgewebes führt.

Key words

osteoarthritis (OA) - transforming growth factor beta 1 (TGFβ1) - subchondral bone - bone remodeling

Schlüsselwörter

Osteoarthritis (OA) - transformierender Wachstumsfaktor Beta 1 (TGFβ1) - subchondraler Knochen - Knochenumbau

Full Text

References

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