Tissue-specific differences in ECM organization and collagen extractability under estrogen deficiency: A comparative study of skin and tendon.

Estrogen deficiency is known to affect connective tissues, yet its impact on collagen organization beyond bone remains insufficiently understood. In this study, we investigated tissue-specific alterations in type I collagen in rat skin and tendon following ovariectomy, with and without alendronate treatment. Native tissues were analyzed in parallel with corresponding crude collagen isolates to distinguish between collagen-related properties and extracellular matrix (ECM)-level contributions. Estrogen deficiency was associated with tissue-dependent changes, with skin exhibiting increased collagen content together with higher acid extractability, while tendon remained comparatively stable. These findings suggest that collagen extractability is influenced not only by collagen abundance but also by ECM-related factors, including matrix composition and organization. Differences between native tissues and isolates are further consistent with selective extraction effects that may be related to fibrillar organization and matrix interactions. Changes in lipid distribution and glycosaminoglycan content were consistent with tissue-specific matrix remodeling. FTIR analysis of amide I band ratios indicated differences consistent with changes in FTIR-detectable molecular organization; however, these observations should be interpreted as indirect indicators due to potential contributions from non-collagenous components and extraction-related effects. Alendronate treatment was associated with condition-dependent changes primarily at the ECM level, affecting collagen extractability and matrix composition without clear evidence of direct modification of collagen secondary structure. Overall, the results suggest that estrogen deficiency is associated with tissue-specific differences in collagen behavior and extractability, likely reflecting combined effects of ECM composition, organization, and extraction selectivity.