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bioRxiv · 10.64898/2026.03.29.713197

Cross-Platform Transcriptomic Validation Identifies SERPINB2 as a Robust Chondrogenic Biomarker and Reveals Coordinated SERPIN Network Activation During Cartilage Lineage Commitment

Gonzalez-Reyes, B. E.·Hernandez-Lopez, E.·Leyva-Gonzalez, G.·Herrera-Camarena, M. C.·Gonzalez-Ruiz, A. G.·Pena-Rodriguez, L. L.·Espinosa-Morales, C.·Rojas-Berges, I.·Villamil-Galvan, R. M.·Estrada-Elorza, M. d. C.·Martinez-Nava, G. A.·Martinez-Mayorga, K.·Cuz-Lemini, M.·Granados-Montiel, J.
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Abstract

ObjectiveTo validate SERPINB2 and SERPINA9 as chondrogenic biomarker candidates across independent transcriptomic platforms and cell sources, to characterise the complete SERPIN expression landscape during kartogenin (KGN)-induced chondrogenic differentiation of human mesenchymal stem cells (hMSCs), and to identify novel SERPIN biomarker candidates and their signalling context during cartilage lineage commitment. DesignMulti-platform transcriptomic analysis across three independent datasets: (i) Affymetrix HGU133+2 microarray of KGN-induced chondrocytes versus undifferentiated hMSCs (ATCC source); (ii) Affymetrix Clariom D whole-transcriptome array of KGN-treated versus control hMSCs from an independent Mexican source (SINREG Laboratories); and (iii) previously published qPCR validation. Differential expression was computed using limma with Benjamini,Hochberg correction. SERPIN-focused cross-platform correlation and targeted pathway analysis were performed. ResultsThe Clariom D dataset yielded 1,869 differentially expressed genes (925 upregulated, 944 downregulated; FDR < 0.05) from 29,124 transcripts tested. SERPINB2 was concordantly upregulated across all three platforms (Clariom D: fold-change [FC] +3.54, FDR = 0.006; HGU133+2: log2FC = +3.29, nominal P = 0.027; qPCR confirmed), establishing it as one of the most reproducible transcriptomic signals in chondrogenic differentiation. In the direct Bone versus Cart comparison, SERPINB2 showed [~]45-fold chondrogenic enrichment (log2FC = -5.45, adjusted P < 0.0001). Cross-platform SERPIN correlation was significant (Pearson r = 0.54, P = 0.0025; n = 29 shared genes). Four additional SERPINs reached genome-wide significance on Clariom D: SERPINE2 (FC +2.57), SERPING1, SERPIND1, and SERPINE1. SERPINA9 was not replicated in the independent SINREG source, identifying it as a context-dependent marker. ConclusionsSERPINB2 is a robust, cross-platform chondrogenic biomarker with translational potential for osteoarthritis (OA) monitoring. The coordinated SERPIN programme activates a multi-layered proteolytic and signalling network during cartilage lineage commitment, positioning SERPINB2 as a functional regulator of the chondro-osteogenic lineage decision.

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Gonzalez-Reyes, B. E., Hernandez-Lopez, E., Leyva-Gonzalez, G., Herrera-Camarena, M. C., Gonzalez-Ruiz, A. G., Pena-Rodriguez, L. L., Espinosa-Morales, C., Rojas-Berges, I., Villamil-Galvan, R. M., Estrada-Elorza, M. d. C., Martinez-Nava, G. A., Martinez-Mayorga, K., Cuz-Lemini, M., Granados-Montiel, J.. 2026-03-31. Cross-Platform Transcriptomic Validation Identifies SERPINB2 as a Robust Chondrogenic Biomarker and Reveals Coordinated SERPIN Network Activation During Cartilage Lineage Commitment. https://doi.org/10.64898/2026.03.29.713197

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